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Tang W, Wu Q, Liang A, Shi J, Chen J, Zhu X, Mao L. The Promise of mRNA Vaccines in Cancer Treatment: Technology, Innovations, Applications, and Future Directions. Crit Rev Oncol Hematol 2025:104772. [PMID: 40412579 DOI: 10.1016/j.critrevonc.2025.104772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2025] [Revised: 05/10/2025] [Accepted: 05/19/2025] [Indexed: 05/27/2025] Open
Abstract
Tumor is a complex disease that seriously threatens human health. Traditional treatment methods have many limitations. In recent years, with the in-depth study of tumor immune mechanisms, the mRNA vaccine, as an innovative immunotherapy strategy, has attracted wide attention due to its unique advantages and great potential. The purpose of this review is to introduce the technical development status of tumor mRNA vaccines, the application progress in a variety of tumors, and the challenges and future development directions, to provide reference for related research. In this paper, we reviewed the recent literature on tumor mRNA vaccines, analyzed the technical progress in structure modification, delivery tools, immunogenicity regulation, and summarized its application in different tumor types, and discussed the current challenges and future development directions. Conclusions: Remarkable progress has been made in structural modification, delivery tool optimization, and immunogenicity regulation of tumor mRNA vaccines, which show good application prospects in the treatment of a variety of tumors. However, the complexity of the tumor microenvironment, the limitation of immune activation, the stability and translation efficiency of mRNA, and the optimization of delivery systems are still challenges. In the future, the application of new technologies, the exploration of combined treatment strategies, and the advancement of personalized medicine will provide new opportunities for the development of tumor mRNA vaccines. With the continuous progress of technology, tumor mRNA vaccines are expected to play an important role in tumor treatment and bring greater well-being to human health.
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Affiliation(s)
- Weixi Tang
- Department of Immunology, School of Medicine, Nantong University, Nantong China; The Second Affiliated Hospital, Guangdong Medical University, Zhanjiang, China
| | - Qianyi Wu
- Department of Immunology, School of Medicine, Nantong University, Nantong China
| | - Anqi Liang
- The Second Affiliated Hospital, Guangdong Medical University, Zhanjiang, China; Department of Oncology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Jiyuan Shi
- Department of Immunology, School of Medicine, Nantong University, Nantong China
| | - Jingru Chen
- The Second Affiliated Hospital, Guangdong Medical University, Zhanjiang, China
| | - Xiao Zhu
- The Second Affiliated Hospital, Guangdong Medical University, Zhanjiang, China.
| | - Liming Mao
- Department of Immunology, School of Medicine, Nantong University, Nantong China.
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Pan M, Cao W, Zhai J, Zheng C, Xu Y, Zhang P. mRNA-based vaccines and therapies - a revolutionary approach for conquering fast-spreading infections and other clinical applications: a review. Int J Biol Macromol 2025; 309:143134. [PMID: 40233916 DOI: 10.1016/j.ijbiomac.2025.143134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 04/10/2025] [Accepted: 04/11/2025] [Indexed: 04/17/2025]
Abstract
Since the beginning of the COVID-19 pandemic, the development of messenger RNA (mRNA) vaccines has made significant progress in the pharmaceutical industry. The two COVID-19 mRNA vaccines from Moderna and Pfizer/BioNTech have been approved for marketing and have made significant contributions to preventing the spread of SARS-CoV-2. In addition, mRNA therapy has brought hope to some diseases that do not have specific treatment methods or are difficult to treat, such as the Zika virus and influenza virus infections, as well as the prevention and treatment of tumors. With the rapid development of in vitro transcription (IVT) technology, delivery systems, and adjuvants, mRNA therapy has also been applied to hereditary diseases such as Fabry's disease. This article reviews the recent development of mRNA vaccines for structural modification, treatment and prevention of different diseases; delivery carriers and adjuvants; and routes of administration to promote the clinical application of mRNA therapies.
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Affiliation(s)
- Mingyue Pan
- Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen 518001, China
| | - Weiling Cao
- Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen 518001, China
| | - Jingbo Zhai
- Key Laboratory of Zoonose Prevention and Control at Universities of Inner Mongolia Autonomous Region, Medical College, Inner Mongolia Minzu University, Tongliao 028000, China
| | - Chunfu Zheng
- Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
| | - Yingying Xu
- Department of Pharmaceutics, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China.
| | - Peng Zhang
- Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen 518001, China.
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3
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Li H, Min L, Du H, Wei X, Tong A. Cancer mRNA vaccines: clinical application progress and challenges. Cancer Lett 2025; 625:217752. [PMID: 40306545 DOI: 10.1016/j.canlet.2025.217752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 04/13/2025] [Accepted: 04/26/2025] [Indexed: 05/02/2025]
Abstract
Messenger RNA (mRNA) vaccines have emerged as one of the most promising and rapidly evolving immunotherapeutic approaches due to their ease of production, demonstrated clinical efficacy, and high safety. The coronavirus disease 2019(COVID-19) pandemic has showcased the remarkable therapeutic potential of mRNA vaccines, prompting researchers to explore their use for cancer treatment. Preclinical studies and human clinical trials have indicated their substantial clinical applicability. However, current research faces several challenges, including the complexity of tumor antigen selection, vaccine stability, and the development of resistance. This review summarizes the optimization strategies for cancer mRNA vaccines in preclinical settings, the progress of clinical trials, and the challenges encountered while analyzing various delivery vehicle types, infusion methods, and application cases across different cancer types, highlighting key factors in vaccine design. The findings demonstrate that mRNA vaccines elicit specific immune responses and exhibit favorable safety and tolerability in clinical trials. Moreover, developing personalized neoantigen vaccines offers a novel direction for cancer immunotherapy. The unique contribution of this review lies in its comprehensive overview of the latest advancements in therapeutic mRNA vaccines for cancer treatment while identifying critical areas for future research to propel the field forward.
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Affiliation(s)
- Hang Li
- State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Lang Min
- Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Haotian Du
- State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Xiawei Wei
- Laboratory of Aging Research and Cancer Drug Target, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Aiping Tong
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
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Wang J, Huang S, Wei H, Liang S, Ding Y, Xiao Z, Shuai X. A dissolvable microneedle platform for the delivery of tumor-derived total RNA nanovaccines for enhanced tumor immunotherapy. Acta Biomater 2025:S1742-7061(25)00294-6. [PMID: 40274056 DOI: 10.1016/j.actbio.2025.04.039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 03/31/2025] [Accepted: 04/21/2025] [Indexed: 04/26/2025]
Abstract
Tumor-derived total RNA (TdRNA) vaccines induce broad immune responses by either synthesizing tumor-specific antigens or activating pattern recognition receptors, making them a promising tool in cancer immunotherapy for the activation of cytotoxic T lymphocytes (CTLs). However, TdRNA vaccines face issues such as low stability and inadequate immune activation. To overcome these challenges, we have developed a dissolvable microneedle delivery platform, PTC NVs@MNs, designed for the simultaneous delivery of TdRNA and CpG oligodeoxynucleotides (CpG ODN). This platform stabilizes TdRNA, maintaining its activity for up to 30 days at room temperature and promotes dendritic cell maturation, and then activates T lymphocyte-mediated antitumor immunity through the targeted delivery of TdRNA and CpG. PTC NVs@MNs not only enhance dendritic cell maturation and increase CD8+ T cell infiltration into tumors, eliciting robust antitumor immune responses that inhibit tumor growth, but also induce antitumor immune memory to prevent tumor development. This innovative approach offers therapeutic and preventive benefits in tumor management. STATEMENT OF SIGNIFICANCE: Tumor-derived total RNA (TdRNA) holds potential for eliciting a broad immune response; however, its therapeutic efficacy against triple-negative breast cancer (TNBC) is constrained by low stability and inadequate immune activation. To overcome these limitations, we engineered a dissolving microneedle patch for transdermal co-delivery of TdRNA and CpG oligodeoxynucleotides (CpG ODN). This system not only stabilizes TdRNA-maintaining its bioactivity for 30 days at room temperature-but also promotes dendritic cell maturation and activates T lymphocyte-mediated antitumor immunity . This study demonstrated that the well-designed microneedle patch effectively prevents RNA degradation without requiring stringent storage conditions, offering both therapeutic and preventive benefits in tumor management.
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Affiliation(s)
- Jiachen Wang
- PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China
| | - Sicong Huang
- PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China
| | - Huiye Wei
- PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China
| | - Simin Liang
- Nanomedicine Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Yuan Ding
- PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China
| | - Zecong Xiao
- Nanomedicine Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
| | - Xintao Shuai
- PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China; Nanomedicine Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
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Paczkowska A, Hoffmann K, Andrzejczak A, Pucek WF, Kopciuch D, Bryl W, Nowakowska E, Kus K. The Application of mRNA Technology for Vaccine Production-Current State of Knowledge. Vaccines (Basel) 2025; 13:389. [PMID: 40333251 PMCID: PMC12031289 DOI: 10.3390/vaccines13040389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 03/27/2025] [Accepted: 03/31/2025] [Indexed: 05/09/2025] Open
Abstract
Over the past 20 years, intensive research has been conducted on the development of therapeutic mRNA, leading to numerous discoveries that have enabled its use in therapy. The main achievements in this field include increasing mRNA stability, reducing its immunogenicity (i.e., its ability to trigger an immune response), and solving the challenge of delivering mRNA into cells-all to achieve a therapeutic effect. The aim of this study was to review the scientific literature on the use of mRNA technology in the production of vaccines. Various methods of applying mRNA technology that could potentially be introduced into clinical practice in the future are described. A detailed analysis was conducted on the approved COVID-19 vaccines developed by Pfizer/BioNTech (New York, NY, USA) and Moderna (Kirkland, QC, Canada), as their introduction marked a groundbreaking moment in the advancement of mRNA technology. This study was based on the latest scientific literature from reputable publishers and medical databases such as PubMed and ClinicalTrials. In conclusion, mRNA technology is currently experiencing rapid development, significantly driven by the ongoing COVID-19 pandemic. The application of this technology holds great potential not only for vaccines against infectious diseases but also for cancer treatment. However, further research is necessary to facilitate its broader clinical implementation.
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Affiliation(s)
- Anna Paczkowska
- Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3 Street, 60-806 Poznan, Poland; (A.A.); (W.F.P.); (D.K.); (K.K.)
| | - Karolina Hoffmann
- Department and Clinic of Internal Diseases and Metabolic Disorders, Poznan University of Medical Sciences, Przybyszewskiego 49 Street, 60-355 Poznan, Poland; (K.H.); (W.B.)
| | - Agata Andrzejczak
- Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3 Street, 60-806 Poznan, Poland; (A.A.); (W.F.P.); (D.K.); (K.K.)
| | - Weronika Faustyna Pucek
- Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3 Street, 60-806 Poznan, Poland; (A.A.); (W.F.P.); (D.K.); (K.K.)
| | - Dorota Kopciuch
- Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3 Street, 60-806 Poznan, Poland; (A.A.); (W.F.P.); (D.K.); (K.K.)
| | - Wiesław Bryl
- Department and Clinic of Internal Diseases and Metabolic Disorders, Poznan University of Medical Sciences, Przybyszewskiego 49 Street, 60-355 Poznan, Poland; (K.H.); (W.B.)
| | - Elżbieta Nowakowska
- Department of Pharmacology and Toxicology Institute of Health Sciences, Collegium Medicum, University of Zielona Gora, Licealna 9 Street, 65-417 Zielona Góra, Poland;
| | - Krzysztof Kus
- Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3 Street, 60-806 Poznan, Poland; (A.A.); (W.F.P.); (D.K.); (K.K.)
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Yang LX, Li H, Cheng ZH, Sun HY, Huang JP, Li ZP, Li XX, Hu ZG, Wang J. The Application of Non-Coding RNAs as Biomarkers, Therapies, and Novel Vaccines in Diseases. Int J Mol Sci 2025; 26:3055. [PMID: 40243658 PMCID: PMC11988403 DOI: 10.3390/ijms26073055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Revised: 03/22/2025] [Accepted: 03/24/2025] [Indexed: 04/18/2025] Open
Abstract
Non-coding RNAs (ncRNAs) are a class of RNAs that largely lack the capacity to encode proteins. They have garnered significant attention due to their central regulatory functions across numerous cellular and physiological processes at transcriptional, post-transcriptional, and translational levels. Over the past decade, ncRNA-based therapies have gained considerable attention in the diagnosis, treatment, and prevention of diseases, and many studies have revealed a significant relationship between ncRNAs and diseases. At the same time, due to their tissue specificity, an increasing number of projects have focused on the application of ncRNAs as biomarkers in diseases, as well as the design and development of novel ncRNA-based vaccines and therapies for clinical use. These ncRNAs may also drive research into the potential molecular mechanisms and complex pathogenesis of related diseases. However, new biomarkers need to be validated for their clinical effectiveness. Additionally, to produce safe and stable RNA products, factors such as purity, precise dosage, and effective delivery methods must be ensured to achieve optimal bioactivity. These challenges remain key issues in the clinical application of ncRNAs. This review summarizes the prospects of ncRNAs as potential biomarkers, as well as the current research status and clinical applications of ncRNAs in therapies and vaccines, and discusses the challenges and expectations of ncRNAs in disease diagnosis and drug therapy.
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Affiliation(s)
- Lu-Xuan Yang
- Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (L.-X.Y.); (H.L.); (Z.-H.C.); (H.-Y.S.); (J.-P.H.); (Z.-P.L.)
| | - Hui Li
- Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (L.-X.Y.); (H.L.); (Z.-H.C.); (H.-Y.S.); (J.-P.H.); (Z.-P.L.)
| | - Zhi-Hui Cheng
- Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (L.-X.Y.); (H.L.); (Z.-H.C.); (H.-Y.S.); (J.-P.H.); (Z.-P.L.)
| | - He-Yue Sun
- Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (L.-X.Y.); (H.L.); (Z.-H.C.); (H.-Y.S.); (J.-P.H.); (Z.-P.L.)
| | - Jie-Ping Huang
- Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (L.-X.Y.); (H.L.); (Z.-H.C.); (H.-Y.S.); (J.-P.H.); (Z.-P.L.)
| | - Zhi-Peng Li
- Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (L.-X.Y.); (H.L.); (Z.-H.C.); (H.-Y.S.); (J.-P.H.); (Z.-P.L.)
| | - Xin-Xin Li
- Institute of Scientific Research, Guangxi University, Nanning 530004, China;
| | - Zhi-Gang Hu
- College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China
| | - Jian Wang
- Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China; (L.-X.Y.); (H.L.); (Z.-H.C.); (H.-Y.S.); (J.-P.H.); (Z.-P.L.)
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Yuan Z, Wang JH, Cui H, Wang SY, Wei B, Cui JX. Mapping the landscape of gastric cancer immunotherapy: Bibliometric insights into advances and hotspots. World J Gastrointest Oncol 2025; 17:100997. [PMID: 40092931 PMCID: PMC11866247 DOI: 10.4251/wjgo.v17.i3.100997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 12/11/2024] [Accepted: 12/31/2024] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Immunotherapy has surfaced as a promising therapeutic modality for gastric cancer (GC). A comprehensive review of advancements, current status, and research trends in GC immunotherapy is essential to inform future investigative efforts. AIM To delineate the trends, advancements, and focal points in immunotherapy for GC. METHODS We performed a bibliometric analysis of 2906 articles in English concerning GC immunotherapy published from 2000 to December 20, 2023, indexed in the Web of Science Core Collection. Data analysis and visualization were facilitated by CiteSpace (6.1.6R), VOSviewer v.1.6.17, and GraphPad Prism v8.0.2. RESULTS There has been an increase in the annual publication rate of GC immunotherapy research. China leads in publication volume, while the United States demonstrates the highest citation impact. Fudan University is notable for its citation frequency and publication output. Co-citation analysis and keyword frequency revealed and highlighted a focus on GC prognosis, the tumor microenvironment (TME), and integrative immunotherapy with targeted therapy. Emerging research areas include gastroesophageal junction cancer, adoptive immunotherapy, and the role of Treg cell in immunotherapy. CONCLUSION GC immunotherapy research is an expanding field attracting considerable scientific interest. With the clinical adoption of immunotherapy in GC, the primary goals are to enhance treatment efficacy and patient outcomes. Unlike hematological malignancies, GC's solid TME presents distinct immunological challenges that may attenuate the cytotoxic effects of immune cells on cancer cells. For instance, although CAR-T therapy is effective in hematological malignancies, it has underperformed in GC settings. Current research is centered on overcoming immunosuppression within the TME, with a focus on combinations of targeted therapy, adoptive immunotherapy, Treg cell dynamics, and precise prognosis prediction in immunotherapy. Additionally, immunotherapy's role in treating gastroesophageal junction cancer has become a novel research focus.
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Affiliation(s)
- Zhen Yuan
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Jing-Hang Wang
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Hao Cui
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Shu-Yuan Wang
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Bo Wei
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Jian-Xin Cui
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
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Imani S, Lv S, Qian H, Cui Y, Li X, Babaeizad A, Wang Q. Current innovations in mRNA vaccines for targeting multidrug-resistant ESKAPE pathogens. Biotechnol Adv 2025; 79:108492. [PMID: 39637949 DOI: 10.1016/j.biotechadv.2024.108492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 10/30/2024] [Accepted: 11/28/2024] [Indexed: 12/07/2024]
Abstract
The prevalence of multidrug-resistant (MDR) ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, represents a critical global public health challenge. In response, mRNA vaccines offer an adaptable and scalable platform for immunotherapy against ESKAPE pathogens by encoding specific antigens that stimulate B-cell-driven antibody production and CD8+ T-cell-mediated cytotoxicity, effectively neutralizing these pathogens and combating resistance. This review examines recent advancements and ongoing challenges in the development of mRNA vaccines targeting MDR ESKAPE pathogens. We explore antigen selection, the nuances of mRNA vaccine technology, and the complex interactions between bacterial infections and antibiotic resistance. By assessing the potential efficacy of mRNA vaccines and addressing key barriers to their paraclinical implementation, this review highlights the promising function of mRNA-based immunization in combating MDR ESKAPE pathogens.
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Affiliation(s)
- Saber Imani
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, Zhejiang, China
| | - Shuojie Lv
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, Zhejiang, China
| | - Hongbo Qian
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, Zhejiang, China
| | - Yulan Cui
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, Zhejiang, China
| | - XiaoYan Li
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, Zhejiang, China
| | - Ali Babaeizad
- Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Qingjing Wang
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, Zhejiang, China.
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Kiełbowski K, Plewa P, Zadworny J, Bakinowska E, Becht R, Pawlik A. Recent Advances in the Development and Efficacy of Anti-Cancer Vaccines-A Narrative Review. Vaccines (Basel) 2025; 13:237. [PMID: 40266115 PMCID: PMC11946321 DOI: 10.3390/vaccines13030237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Revised: 02/19/2025] [Accepted: 02/24/2025] [Indexed: 04/24/2025] Open
Abstract
Immunotherapy is an established and efficient treatment strategy for a variety of malignancies. It aims to boost the anticancer properties of one's own immune system. Several immunotherapeutic options are available, but immune checkpoint blockers represent the most widely known and investigated. Anticancer vaccines represent an evolving area of immunotherapy that stimulate antigen-presenting cells, cytotoxic responses of CD8+ T cells, and the presence of memory T cells, among others. Over the years, different approaches for anticancer vaccines have been studied, such as mRNA and DNA vaccines, together with dendritic cell- and viral vector-based vaccines. Recently, an accumulating number of clinical studies have been performed to analyze the safety and potential efficacy of these agents. The aim of this review is to summarize recent advances regarding different types of therapeutic anticancer vaccines. Furthermore, it will discuss how recent advances in preclinical models can enhance clinical outcomes.
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Affiliation(s)
- Kajetan Kiełbowski
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.); (J.Z.); (E.B.)
- Department of Clinical Oncology, Chemotherapy and Cancer Immunotherapy, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland;
| | - Paulina Plewa
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.); (J.Z.); (E.B.)
| | - Jan Zadworny
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.); (J.Z.); (E.B.)
| | - Estera Bakinowska
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.); (J.Z.); (E.B.)
| | - Rafał Becht
- Department of Clinical Oncology, Chemotherapy and Cancer Immunotherapy, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland;
| | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (P.P.); (J.Z.); (E.B.)
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10
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Koren L, Koren A, Likić R, Katanec T. Revolutionizing Dentistry: Preclinical Insights and Future Applications of mRNA Vaccines in Dentistry-A Narrative Review. Dent J (Basel) 2025; 13:79. [PMID: 39996953 PMCID: PMC11854559 DOI: 10.3390/dj13020079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/16/2025] [Accepted: 02/06/2025] [Indexed: 02/26/2025] Open
Abstract
Background: Recent advances in mRNA vaccine technology, accelerated by the global COVID-19 pandemic, have generated significant interest in their applications beyond infectious diseases. Dentistry has emerged as a promising field for exploring the potential of mRNA-based therapies in preventing and treating oral diseases. Objectives: This narrative review aims to evaluate the current status of mRNA vaccine development and its preclinical applications in oral health, focusing on periodontal disease, dental caries, regenerative medicine, implantology, and oral cancer. Methods: The review synthesizes findings from preclinical studies, including research conducted in animal models and in vitro, to assess the potential of mRNA-based therapies to modulate immune responses and promote tissue regeneration in the oral cavity. Clinical trials were only mentioned in the context of broader areas of mRNA vaccine implementation such as oncology and immunotherapy. Results: The preclinical studies highlight the capacity of mRNA vaccines to enhance the body's immune response and facilitate tissue repair processes. Despite these promising results, challenges persist in delivering mRNA vaccines effectively within the complex oral environment. These challenges include vaccine stability, delivery mechanisms, and the modulation of immune responses. Conclusions: While mRNA vaccines offer significant promise for revolutionizing oral health care, they face notable limitations concerning safety, efficacy, and clinical feasibility. Overcoming these obstacles through further research is essential to unlock their full translational potential and ensure their safe and effective integration into dental practice.
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Affiliation(s)
- Luciana Koren
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.K.); (A.K.)
| | - Andro Koren
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia; (L.K.); (A.K.)
| | - Robert Likić
- Unit for Clinical Pharmacology, Department of Internal Medicine, Clinical Hospital Centre Zagreb, 10000 Zagreb, Croatia;
| | - Tomislav Katanec
- Department of Oral Surgery, School of Dental Medicine Zagreb, Clinical Hospital Centre Zagreb, 10000 Zagreb, Croatia
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11
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Mehta A, Motavaf M, Nebo I, Luyten S, Osei-Opare KD, Gru AA. Advancements in Melanoma Treatment: A Review of PD-1 Inhibitors, T-VEC, mRNA Vaccines, and Tumor-Infiltrating Lymphocyte Therapy in an Evolving Landscape of Immunotherapy. J Clin Med 2025; 14:1200. [PMID: 40004731 PMCID: PMC11856346 DOI: 10.3390/jcm14041200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 02/08/2025] [Accepted: 02/11/2025] [Indexed: 02/27/2025] Open
Abstract
Melanoma, an aggressive skin cancer, presents significant therapeutic challenges. Consequently, innovative treatment strategies beyond conventional chemotherapy, radiation, and surgery are actively explored. This review discusses the evolution of immunotherapy in advanced melanoma, highlighting PD-1/PD-L1 inhibitors, mRNA vaccines, Talimogene Laherparepvec (T-VEC), and tumor-infiltrating lymphocyte (TIL) therapies. PD-1/PD-L1 inhibitors such as pembrolizumab and nivolumab block immune checkpoints, promoting T-cell cytotoxic activity and improving overall survival in patients with advanced melanoma. T-VEC, a modified oncolytic herpes virus, promotes a systemic anti-tumor response while simultaneously lysing malignant cells. mRNA vaccines, such as Moderna's mRNA-4157/V940, take advantage of malignant-cell-specific neoantigens to amplify the adaptive immune response while protecting healthy tissue. TIL therapy is a form of therapy involving ex vivo expansion and reinfusion of the patient's tumor-specific lymphocytes and has been shown to provide durable tumor control. While these therapies have demonstrated promising clinical outcomes, challenges such as tumor resistance, high financial burden, and limited accessibility pose challenges to their widespread use. This review explores combination therapies such as PD-L1 inhibitors with mRNA vaccines, or TIL therapy, which aim to enhance treatment through synergistic approaches. Further research is required to optimize these combinations, address barriers preventing their use, and control adverse events.
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Affiliation(s)
- Apoorva Mehta
- Columbia University Vagelos College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA; (I.N.); (S.L.); (K.D.O.-O.)
| | - Mateen Motavaf
- Duke University School of Medicine, Durham, NC 27710, USA;
| | - Ikenna Nebo
- Columbia University Vagelos College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA; (I.N.); (S.L.); (K.D.O.-O.)
| | - Sophia Luyten
- Columbia University Vagelos College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA; (I.N.); (S.L.); (K.D.O.-O.)
| | - Kofi D. Osei-Opare
- Columbia University Vagelos College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA; (I.N.); (S.L.); (K.D.O.-O.)
| | - Alejandro A. Gru
- Department of Dermatology, Columbia University Irving Medical Center, New York, NY 10032, USA;
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12
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Mutchek S, Kenderdine T, Turner K, Ring J, German M, Fabris D. Strand-Cleaving Deoxyribozymes Enable the Mid-Down Sequencing of mRNA by Mass Spectrometry with No Front-End Separations. Anal Chem 2025; 97:2972-2980. [PMID: 39888840 DOI: 10.1021/acs.analchem.4c05860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2025]
Abstract
We evaluated the possible application of RNA-cleaving deoxyribozymes to control the number and size of cleavage products obtained during the mid-down characterization of larger nucleic acids by mass spectrometry (MS). We assessed the structural determinants of substrate selectivity, as well as the effects of cofactor, additives, and environmental parameters on the cleavage activity of the histidine-dependent deoxyribozyme 3 (HD3). We designed dedicated sets of HD3 variants capable of cleaving RNA strands as large as the 758 nt enhanced green fluorescent protein (eGFP) mRNA. This substrate was dissected into only 10 oligonucleotides with lengths ranging from 46 to 120 nt, which compared favorably with the 87 unique products ranging from 3 to 14 nt to be expected instead from putative RNase T1 digestion. The complexity of such mixture was sufficiently limited to enable its comprehensive analysis by direct infusion nanospray-MS without front-end separation. Their unambiguous assignment was accomplished by matching experimental with predicted masses, which revealed the formation of mis-cleaved products and enabled the mass mapping of 100% of the initial substrate. Product identity was verified by collision-induced dissociation (CID), which provided individual sequence coverages ranging from 87 to 100%, with the lower figure obtained from a 120 nt mis-cleaved product. All sequence information combined accounted for 95% coverage of the 758 nt substrate, but without all the ambiguities engendered by classic nucleotide-specific endonucleases. This outcome demonstrated the feasibility of mid-down approaches based on deoxyribozymes and underscored their potential in the analysis of larger RNAs.
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Affiliation(s)
- Sarah Mutchek
- Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States
| | - Thomas Kenderdine
- Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States
| | - Kevin Turner
- Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, Maryland 21250, United States
| | - Joseph Ring
- Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, Maryland 21250, United States
| | - Michael German
- Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, Maryland 21250, United States
| | - Daniele Fabris
- Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States
- RiboDynamics, Manchester, Connecticut 06040, United States
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13
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Liao HC, Liu SJ. Advances in nucleic acid-based cancer vaccines. J Biomed Sci 2025; 32:10. [PMID: 39833784 PMCID: PMC11748563 DOI: 10.1186/s12929-024-01102-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 11/05/2024] [Indexed: 01/22/2025] Open
Abstract
Nucleic acid vaccines have emerged as crucial advancements in vaccine technology, particularly highlighted by the global response to the COVID-19 pandemic. The widespread administration of mRNA vaccines against COVID-19 to billions globally marks a significant milestone. Furthermore, the approval of an mRNA vaccine for Respiratory Syncytial Virus (RSV) this year underscores the versatility of this technology. In oncology, the combination of mRNA vaccine encoding neoantigens and immune checkpoint inhibitors (ICIs) has shown remarkable efficacy in eliciting protective responses against diseases like melanoma and pancreatic cancer. Although the use of a COVID-19 DNA vaccine has been limited to India, the inherent stability at room temperature and cost-effectiveness of DNA vaccines present a viable option that could benefit developing countries. These advantages may help DNA vaccines address some of the challenges associated with mRNA vaccines. Currently, several trials are exploring the use of DNA-encoded neoantigens in combination with ICIs across various cancer types. These studies highlight the promising role of nucleic acid-based vaccines as the next generation of immunotherapeutic agents in cancer treatment. This review will delve into the recent advancements and current developmental status of both mRNA and DNA-based cancer vaccines.
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Affiliation(s)
- Hung-Chun Liao
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, 35053, Taiwan
| | - Shih-Jen Liu
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, 35053, Taiwan.
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 406040, Taiwan.
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 307378, Taiwan.
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14
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Fu Q, Zhao X, Hu J, Jiao Y, Yan Y, Pan X, Wang X, Jiao F. mRNA vaccines in the context of cancer treatment: from concept to application. J Transl Med 2025; 23:12. [PMID: 39762875 PMCID: PMC11702060 DOI: 10.1186/s12967-024-06033-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 12/24/2024] [Indexed: 01/11/2025] Open
Abstract
Immuno-oncology has witnessed remarkable advancements in the past decade, revolutionizing the landscape of cancer therapeutics in an encouraging manner. Among the diverse immunotherapy strategies, mRNA vaccines have ushered in a new era for the therapeutic management of malignant diseases, primarily due to their impressive impact on the COVID-19 pandemic. In this comprehensive review, we offer a systematic overview of mRNA vaccines, focusing on the optimization of structural design, the crucial role of delivery materials, and the administration route. Additionally, we summarize preclinical studies and clinical trials to provide valuable insights into the current status of mRNA vaccines in cancer treatment. Furthermore, we delve into a systematic discussion on the significant challenges facing the current development of mRNA tumor vaccines. These challenges encompass both intrinsic and external factors that are closely intertwined with the successful application of this innovative approach. To pave the way for a more promising future in cancer treatments, a deeper understanding of immunological mechanisms, an increasing number of high-quality clinical trials, and a well-established manufacturing platform are crucial. Collaborative efforts between scientists, clinicians, and industry engineers are essential to achieving these goals.
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Affiliation(s)
- Qiang Fu
- School of Pharmacology, Institute of Aging Medicine, Binzhou Medical University, Yantai, 264003, P. R. China
| | - Xiaoming Zhao
- Center of Physical Examination, Binzhou Medical University Affiliated 970 Hospital of the PLA Joint Logistic Support Force, Yantai, 264002, P. R. China
| | - Jinxia Hu
- Department of Biochemistry and Molecular Biology, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, P. R. China
| | - Yang Jiao
- Department of Biomedical Engineering, Faculty of Engineering, The Hong Kong Polytechnic University, Hong Kong, 999077, P. R. China
| | - Yunfei Yan
- Department of Biochemistry and Molecular Biology, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, P. R. China
| | - Xuchen Pan
- Department of Clinical Laboratory & Health Service Training, Binzhou Medical University Affiliated 970 Hospital of the PLA Joint Logistic Support Force, Yantai, 264002, P. R. China
| | - Xin Wang
- Department of Clinical Laboratory & Health Service Training, Binzhou Medical University Affiliated 970 Hospital of the PLA Joint Logistic Support Force, Yantai, 264002, P. R. China.
| | - Fei Jiao
- Department of Biochemistry and Molecular Biology, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, P. R. China.
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15
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Wang C, Zhang X, Li Q, Hou Y, Sun M, Sun J, Lou Z, Han X, Li Y. A review of carbohydrate polymer-synthesized nanoparticles in cancer immunotherapy: Past, present and future perspectives. Int J Biol Macromol 2025; 286:138195. [PMID: 39645110 DOI: 10.1016/j.ijbiomac.2024.138195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 11/19/2024] [Accepted: 11/28/2024] [Indexed: 12/09/2024]
Abstract
Cancer continues to be a leading factor in mortality and tackling it has been made difficult by the development of immune escape. Furthermore, alternative treatments like surgery, chemotherapy, and radiation have been unsuccessful in eradicating cancer. Despite being effective, they have not succeeded in providing a full cancer treatment and exhibit several negative effects. The field of immunotherapy has been improved by utilizing cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive cell transfer to enhance immune responses to tumors. Nevertheless, cancer cells need to adapt and become immune to immune reactions, leading to the need for innovative treatment methods. Carbohydrate polymers and their nanoparticles have been beneficial in improving cancer immunotherapy by being customizable to specifically target the immune system. These nanoparticles can change the tumor microenvironment and accelerate immunotherapy by affecting immune cells such as T cells and dendritic cells. Incorporating both chemotherapy and phototherapy into nanoparticles can improve immunotherapy. Furthermore, besides controlling immune reactions, carbohydrate polymer nanoparticles can also be used for theranostic purposes, where they are used to image tumor cells and activate the immune system to eradicate cancer.
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Affiliation(s)
- Chunyan Wang
- Department of Ultrasonic Diagnosis, The First Hospital of China Medical University, Shenyang, China
| | - Xueyao Zhang
- Department of Cardiology, First Hospital of China Medical University, Shenyang, China
| | - Qiaobei Li
- Department of Ultrasonic Diagnosis, The First Hospital of China Medical University, Shenyang, China
| | - Yuxin Hou
- Department of Ultrasonic Diagnosis, The Benxi Hospital of China Medical University, Benxi, China
| | - Minglu Sun
- Department of Ultrasonic Diagnosis, The Cancer Hospital of China Medical University, Shenyang, China
| | - Jun Sun
- Department of Intervention, the Fourth Hospital of China Medical University, Shenyang, China
| | - Zhe Lou
- Department of Cardiovascular Ultrasonic Diagnosis, The First Hospital of China Medical University, Shenyang, China.
| | - Xu Han
- Department of Traditional Chinese medicine, The First Hospital of China Medical University, Shenyang, China.
| | - Yinyan Li
- Department of Ultrasonic Diagnosis, The First Hospital of China Medical University, Shenyang, China.
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16
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Zhang C, Wang Y, Peng J, Wen X, Zhang Y, Li K, Du H, Hu X. Decoding trends in mRNA vaccine research: A comprehensive bibliometric study. Hum Vaccin Immunother 2024; 20:2355037. [PMID: 38813652 PMCID: PMC11141478 DOI: 10.1080/21645515.2024.2355037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 05/10/2024] [Indexed: 05/31/2024] Open
Abstract
BACKGROUND In recent years, infectious diseases like COVID-19 have had profound global socio-economic impacts. mRNA vaccines have gained prominence due to their rapid development, industrial adaptability, simplicity, and responsiveness to new variants. Notably, the 2023 Nobel Prize in Physiology or Medicine recognized significant contributions to mRNA vaccine research. METHODS Our study employed a comprehensive bibliometric analysis using the Web of Science Core Collection (WoSCC) database, encompassing 5,512 papers on mRNA vaccines from 2003 to 2023. We generated cooperation maps, co-citation analyses, and keyword clustering to evaluate the field's developmental history and achievements. RESULTS The analysis yielded knowledge maps highlighting countries/institutions, influential authors, frequently published and highly cited journals, and seminal references. Ongoing research hotspots encompass immune responses, stability enhancement, applications in cancer prevention and treatment, and combating infectious diseases using mRNA technology. CONCLUSIONS mRNA vaccines represent a transformative development in infectious disease prevention. This study provides insights into the field's growth and identifies key research priorities, facilitating advancements in vaccine technology and addressing future challenges.
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Affiliation(s)
- Chaobin Zhang
- Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Yuhang Wang
- School of Basic Medicine, Capital Medical University, Beijing, China
| | - Jianding Peng
- School of Basic Medicine, Capital Medical University, Beijing, China
| | - Xiaotian Wen
- School of Basic Medicine, Capital Medical University, Beijing, China
| | - Youwen Zhang
- School of Law, City University of Hongkong, Hong Kong, China
| | - Kejun Li
- Department of Library, Chongqing Vocational Institute of Engineering, Chongqing, China
| | - Hanjian Du
- Department of Neurosurgery, Chongqing Research Center for Glioma Precision Medicine, Chongqing General Hospital, Chongqing University, Chongqing, China
| | - Xiaofei Hu
- Department of Nuclear Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
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17
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Yao R, Xie C, Xia X. Recent progress in mRNA cancer vaccines. Hum Vaccin Immunother 2024; 20:2307187. [PMID: 38282471 PMCID: PMC10826636 DOI: 10.1080/21645515.2024.2307187] [Citation(s) in RCA: 37] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 01/16/2024] [Indexed: 01/30/2024] Open
Abstract
The research and development of messenger RNA (mRNA) cancer vaccines have gradually overcome numerous challenges through the application of personalized cancer antigens, structural optimization of mRNA, and the development of alternative RNA-based vectors and efficient targeted delivery vectors. Clinical trials are currently underway for various cancer vaccines that encode tumor-associated antigens (TAAs), tumor-specific antigens (TSAs), or immunomodulators. In this paper, we summarize the optimization of mRNA and the emergence of RNA-based expression vectors in cancer vaccines. We begin by reviewing the advancement and utilization of state-of-the-art targeted lipid nanoparticles (LNPs), followed by presenting the primary classifications and clinical applications of mRNA cancer vaccines. Collectively, mRNA vaccines are emerging as a central focus in cancer immunotherapy, offering the potential to address multiple challenges in cancer treatment, either as standalone therapies or in combination with current cancer treatments.
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Affiliation(s)
- Ruhui Yao
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chunyuan Xie
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiaojun Xia
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China
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18
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Shi R, Ran L, Tian Y, Guo W, Zhao L, Jin S, Cheng J, Zhang Z, Ma Y. Prospects and challenges of neoantigen applications in oncology. Int Immunopharmacol 2024; 143:113329. [PMID: 39405926 DOI: 10.1016/j.intimp.2024.113329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 09/11/2024] [Accepted: 10/02/2024] [Indexed: 10/30/2024]
Abstract
Neoantigen, unique peptides resulting from tumor-specific mutations, represent a promising frontier in oncology for personalized cancer immunotherapy. Their unique features allow for the development of highly specific and effective cancer treatments, which can potentially overcome the limitations of conventional therapies. This paper explores the current prospects and challenges associated with the application of neoantigens in oncology. We examine the latest advances in neoantigen identification, vaccine development, and adoptive T cell therapy. Additionally, we discuss the obstacles related to neoantigen heterogeneity, immunogenicity prediction, and the tumor microenvironment. Through a comprehensive analysis of current research and clinical trials, this paper aims to provide a detailed overview of how neoantigens could revolutionize cancer treatment and the hurdles that must be overcome to realize their full potential.
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Affiliation(s)
- Ranran Shi
- Department of Basic Medical Sciences, Luohe Medical College, Luohe 462000, China; Henan Province Engineering & Technology Research Center of Foods for Special Medical Purpose, Luohe Medical College, Luohe 462000, China
| | - Ling Ran
- Department of Basic Medical Sciences, Luohe Medical College, Luohe 462000, China; Henan Province Engineering & Technology Research Center of Foods for Special Medical Purpose, Luohe Medical College, Luohe 462000, China
| | - Yuan Tian
- Department of Basic Medical Sciences, Luohe Medical College, Luohe 462000, China; Henan Province Engineering & Technology Research Center of Foods for Special Medical Purpose, Luohe Medical College, Luohe 462000, China
| | - Wei Guo
- Department of Basic Medical Sciences, Luohe Medical College, Luohe 462000, China
| | - Lifang Zhao
- Department of Basic Medical Sciences, Luohe Medical College, Luohe 462000, China; Henan Province Engineering & Technology Research Center of Foods for Special Medical Purpose, Luohe Medical College, Luohe 462000, China
| | - Shaoju Jin
- Department of Basic Medical Sciences, Luohe Medical College, Luohe 462000, China; Henan Province Engineering & Technology Research Center of Foods for Special Medical Purpose, Luohe Medical College, Luohe 462000, China
| | - Jiang Cheng
- Department of Basic Medical Sciences, Luohe Medical College, Luohe 462000, China; Department of Neurology, General Hospital of Ningxia Medical University, Yinchuan 750000, China
| | - Zhe Zhang
- School of Sciences, Henan University of Technology, Zhengzhou 450001, China.
| | - Yongchao Ma
- Department of Basic Medical Sciences, Luohe Medical College, Luohe 462000, China.
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19
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Du H, Chen HB, Zhao Y. Exploring a new chapter in traditional Chinese medicine: The potential of Calculus bovis in liver cancer treatment. World J Clin Oncol 2024; 15:1520-1527. [PMID: 39720650 PMCID: PMC11514369 DOI: 10.5306/wjco.v15.i12.1520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 09/19/2024] [Accepted: 10/15/2024] [Indexed: 10/22/2024] Open
Abstract
In the ongoing quest for new treatments in medicine, traditional Chinese medicine offers unique insights and potential. Recently, studies on the ability of Calculus bovis to inhibit M2-type tumour-associated macrophage polarisation by modulating the Wnt/β-catenin signalling pathway to suppress liver cancer have undoubtedly revealed new benefits and hope for this field of research. The purpose of this article is to comment on this study and explore its strengths and weaknesses, thereby providing ideas for the future treatment of liver cancer.
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Affiliation(s)
- Huang Du
- Department of Gastroenterology, Minqing County General Hospital, Fuzhou 350800, Fujian Province, China
| | - Hong-Bin Chen
- Department of Gastroenterology I, Sanming First Hospital, Fujian Medical University, Sanming 365000, Fujian Province, China
| | - Yu Zhao
- Department of Gastroenterology, Hannover Medical School, Carl-Neuberg-Straße 1, Hannover 30625, Lower Saxony, Germany
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20
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Shariati A, Khani P, Nasri F, Afkhami H, Khezrpour A, Kamrani S, Shariati F, Alavimanesh S, Modarressi MH. mRNA cancer vaccines from bench to bedside: a new era in cancer immunotherapy. Biomark Res 2024; 12:157. [PMID: 39696625 DOI: 10.1186/s40364-024-00692-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 11/15/2024] [Indexed: 12/20/2024] Open
Abstract
Harnessing the power of the immune system to target cancer cells is one of the most appealing approaches for cancer therapy. Among these immunotherapies, messenger ribonucleic acid (mRNA) cancer vaccines are worthy of consideration, as they have demonstrated promising results in clinical trials. These vaccines have proven to be safe and well-tolerated. They can be easily mass-produced in a relatively short time and induce a systemic immune response effective against both the primary tumor and metastases. Transcripts encoding immunomodulatory molecules can also be incorporated into the mRNA, enhancing its efficacy. On the other hand, there are some challenges associated with their application, including mRNA instability, insufficient uptake by immune cells, and intrinsic immunogenicity, which can block mRNA translation. Many innovations have been suggested to overcome these obstacles, including structural modification (such as 5' cap modification), optimizing delivery vehicles (especially dendritic cells (DCs) and nanoparticles), and using antigens that can enhance immunogenicity by circumventing tolerance mechanisms. A popular approach is to combine mRNA cancer vaccines with traditional and novel cancer treatments like chemotherapy, radiotherapy, and immune checkpoint blockade (ICB). They are most efficacious when combined with other therapies like ICBs. There is still a long way to go before these vaccines enter the standard of care for cancer patients, but with the incredible pace of development in this field, their clinical application will soon be witnessed. This review highlights the recent advances and challenges of mRNA cancer vaccines. Finally, some of the most prominent clinical applications of these vaccines will be reviewed.
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Affiliation(s)
- Alireza Shariati
- School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Pouria Khani
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Farzad Nasri
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Hamed Afkhami
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran
- Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran
- Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran
| | - Arya Khezrpour
- School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Sina Kamrani
- Department of Orthopedic, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Fatemeh Shariati
- Department of Genetics, North Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Sajad Alavimanesh
- Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran.
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
| | - Mohammad Hossein Modarressi
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
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21
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Yang R, Cui J. Advances and applications of RNA vaccines in tumor treatment. Mol Cancer 2024; 23:226. [PMID: 39385255 PMCID: PMC11463124 DOI: 10.1186/s12943-024-02141-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 09/30/2024] [Indexed: 10/12/2024] Open
Abstract
Compared to other types of tumor vaccines, RNA vaccines have emerged as promising alternatives to conventional vaccine therapy due to their high efficiency, rapid development capability, and potential for low-cost manufacturing and safe drug delivery. RNA vaccines mainly include mRNA, circular RNA (circRNA), and Self-amplifying mRNA(SAM). Different RNA vaccine platforms for different tumors have shown encouraging results in animal and human models. This review comprehensively describes the advances and applications of RNA vaccines in antitumor therapy. Future directions for extending this promising vaccine platform to a wide range of therapeutic uses are also discussed.
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Affiliation(s)
- Ruohan Yang
- Cancer Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Jiuwei Cui
- Cancer Center, The First Hospital of Jilin University, Changchun, 130021, China.
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22
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Cao Q, Fang H, Tian H. mRNA vaccines contribute to innate and adaptive immunity to enhance immune response in vivo. Biomaterials 2024; 310:122628. [PMID: 38820767 DOI: 10.1016/j.biomaterials.2024.122628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 05/02/2024] [Accepted: 05/19/2024] [Indexed: 06/02/2024]
Abstract
Messenger RNA (mRNA) therapeutics have been widely employed as strategies for the treatment and prevention of diseases. Amid the global outbreak of COVID-19, mRNA vaccines have witnessed rapid development. Generally, in the case of mRNA vaccines, the initiation of the innate immune system serves as a prerequisite for triggering subsequent adaptive immune responses. Critical cells, cytokines, and chemokines within the innate immune system play crucial and beneficial roles in coordinating tailored immune reactions towards mRNA vaccines. Furthermore, immunostimulators and delivery systems play a significant role in augmenting the immune potency of mRNA vaccines. In this comprehensive review, we systematically delineate the latest advancements in mRNA vaccine research, present an in-depth exploration of strategies aimed at amplifying the immune effectiveness of mRNA vaccines, and offer some perspectives and recommendations regarding the future advancements in mRNA vaccine development.
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Affiliation(s)
- Qiannan Cao
- State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China
| | - Huapan Fang
- State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China; Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen, 361005, China; Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, 215123, China.
| | - Huayu Tian
- State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China; Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen, 361005, China.
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Tapescu I, Madsen PJ, Lowenstein PR, Castro MG, Bagley SJ, Fan Y, Brem S. The transformative potential of mRNA vaccines for glioblastoma and human cancer: technological advances and translation to clinical trials. Front Oncol 2024; 14:1454370. [PMID: 39399167 PMCID: PMC11466887 DOI: 10.3389/fonc.2024.1454370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Accepted: 09/09/2024] [Indexed: 10/15/2024] Open
Abstract
Originally devised for cancer control, mRNA vaccines have risen to the forefront of medicine as effective instruments for control of infectious disease, notably their pivotal role in combating the COVID-19 pandemic. This review focuses on fundamental aspects of the development of mRNA vaccines, e.g., tumor antigens, vector design, and precise delivery methodologies, - highlighting key technological advances. The recent, promising success of personalized mRNA vaccines against pancreatic cancer and melanoma illustrates the potential value for other intractable, immunologically resistant, solid tumors, such as glioblastoma, as well as the potential for synergies with a combinatorial, immunotherapeutic approach. The impact and progress in human cancer, including pancreatic cancer, head and neck cancer, bladder cancer are reviewed, as are lessons learned from first-in-human CAR-T cell, DNA and dendritic cell vaccines targeting glioblastoma. Going forward, a roadmap is provided for the transformative potential of mRNA vaccines to advance cancer immunotherapy, with a particular focus on the opportunities and challenges of glioblastoma. The current landscape of glioblastoma immunotherapy and gene therapy is reviewed with an eye to combinatorial approaches harnessing RNA science. Preliminary preclinical and clinical data supports the concept that mRNA vaccines could be a viable, novel approach to prolong survival in patients with glioblastoma.
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Affiliation(s)
- Iulia Tapescu
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Peter J. Madsen
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
- Division of Neurosurgery, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
- Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States
| | - Pedro R. Lowenstein
- Department of Neurosurgery, The University of Michigan, Ann Arbor, MI, United States
- Department of Cell and Developmental Biology, The University of Michigan, Ann Arbor, MI, United States
- Department of Biomedical Engineering, The University of Michigan, Ann Arbor, MI, United States
| | - Maria G. Castro
- Department of Neurosurgery, The University of Michigan, Ann Arbor, MI, United States
- Department of Cell and Developmental Biology, The University of Michigan, Ann Arbor, MI, United States
| | - Stephen J. Bagley
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
- Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States
- Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United States
| | - Yi Fan
- Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United States
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, United States
| | - Steven Brem
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
- Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States
- Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United States
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24
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Liu Y, Zhang N, Wen Y, Wen J. Head and neck cancer: pathogenesis and targeted therapy. MedComm (Beijing) 2024; 5:e702. [PMID: 39170944 PMCID: PMC11338281 DOI: 10.1002/mco2.702] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 08/02/2024] [Accepted: 08/05/2024] [Indexed: 08/23/2024] Open
Abstract
Head and neck cancer (HNC) is a highly aggressive type of tumor characterized by delayed diagnosis, recurrence, metastasis, relapse, and drug resistance. The occurrence of HNC were associated with smoking, alcohol abuse (or both), human papillomavirus infection, and complex genetic and epigenetic predisposition. Currently, surgery and radiotherapy are the standard treatments for most patients with early-stage HNC. For recurrent or metastatic (R/M) HNC, the first-line treatment is platinum-based chemotherapy combined with the antiepidermal growth factor receptor drug cetuximab, when resurgery and radiation therapy are not an option. However, curing HNC remains challenging, especially in cases with metastasis. In this review, we summarize the pathogenesis of HNC, including genetic and epigenetic changes, abnormal signaling pathways, and immune regulation mechanisms, along with all potential therapeutic strategies such as molecular targeted therapy, immunotherapy, gene therapy, epigenetic modifications, and combination therapies. Recent preclinical and clinical studies that may offer therapeutic strategies for future research on HNC are also discussed. Additionally, new targets and treatment methods, including antibody-drug conjugates, photodynamic therapy, radionuclide therapy, and mRNA vaccines, have shown promising results in clinical trials, offering new prospects for the treatment of HNC.
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Affiliation(s)
- Yan Liu
- Frontiers Medical CenterTianfu Jincheng LaboratoryChengduChina
- National Facility for Translational Medicine (Sichuan)West China Hospital of Sichuan UniversityChengduChina
| | - Nannan Zhang
- National Center for Birth Defect MonitoringKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenMinistry of EducationWest China Second University HospitalSichuan UniversityChengduChina
| | - Yi Wen
- State Key Laboratory of BiotherapyWest China Hospital of Sichuan UniversityChengduChina
| | - Jiaolin Wen
- Frontiers Medical CenterTianfu Jincheng LaboratoryChengduChina
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25
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Gao Y, Yang L, Li Z, Peng X, Li H. mRNA vaccines in tumor targeted therapy: mechanism, clinical application, and development trends. Biomark Res 2024; 12:93. [PMID: 39217377 PMCID: PMC11366172 DOI: 10.1186/s40364-024-00644-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 08/20/2024] [Indexed: 09/04/2024] Open
Abstract
Malignant tumors remain a primary cause of human mortality. Among the various treatment modalities for neoplasms, tumor vaccines have consistently shown efficacy and promising potential. These vaccines offer advantages such as specificity, safety, and tolerability, with mRNA vaccines representing promising platforms. By introducing exogenous mRNAs encoding antigens into somatic cells and subsequently synthesizing antigens through gene expression systems, mRNA vaccines can effectively induce immune responses. Katalin Karikó and Drew Weissman were awarded the 2023 Nobel Prize in Physiology or Medicine for their great contributions to mRNA vaccine research. Compared with traditional tumor vaccines, mRNA vaccines have several advantages, including rapid preparation, reduced contamination, nonintegrability, and high biodegradability. Tumor-targeted therapy is an innovative treatment modality that enables precise targeting of tumor cells, minimizes damage to normal tissues, is safe at high doses, and demonstrates great efficacy. Currently, targeted therapy has become an important treatment option for malignant tumors. The application of mRNA vaccines in tumor-targeted therapy is expanding, with numerous clinical trials underway. We systematically outline the targeted delivery mechanism of mRNA vaccines and the mechanism by which mRNA vaccines induce anti-tumor immune responses, describe the current research and clinical applications of mRNA vaccines in tumor-targeted therapy, and forecast the future development trends of mRNA vaccine application in tumor-targeted therapy.
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Affiliation(s)
- Yu Gao
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Liang Yang
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Zhenning Li
- Department of Oromaxillofacial-Head and Neck Surgery, School and Hospital of Stomatology, China Medical University, Liaoning Province Key Laboratory of Oral Disease, Shenyang, 110001, China
| | - Xueqiang Peng
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China.
| | - Hangyu Li
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China.
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26
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Sui C, Wu H, Li X, Wang Y, Wei J, Yu J, Wu X. Cancer immunotherapy and its facilitation by nanomedicine. Biomark Res 2024; 12:77. [PMID: 39097732 PMCID: PMC11297660 DOI: 10.1186/s40364-024-00625-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 07/22/2024] [Indexed: 08/05/2024] Open
Abstract
Cancer immunotherapy has sparked a wave of cancer research, driven by recent successful proof-of-concept clinical trials. However, barriers are emerging during its rapid development, including broad adverse effects, a lack of reliable biomarkers, tumor relapses, and drug resistance. Integration of nanomedicine may ameliorate current cancer immunotherapy. Ultra-large surface-to-volume ratio, extremely small size, and easy modification surface of nanoparticles enable them to selectively detect cells and kill cancer cells in vivo. Exciting synergistic applications of the two approaches have emerged in treating various cancers at the intersection of cancer immunotherapy and cancer nanomedicine, indicating the potential that the combination of these two therapeutic modalities can lead to new paradigms in the treatment of cancer. This review discusses the status of current immunotherapy and explores the possible opportunities that the nanomedicine platform can make cancer immunotherapy more powerful and precise by synergizing the two approaches.
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Affiliation(s)
- Chao Sui
- Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, 1500 East Duarte, Los Angeles, CA, 91010, USA
| | - Heqing Wu
- The First Affiliated Hospital of Soochow University, Suzhou, China
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Suzhou, China
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
| | - Xinxin Li
- Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an Shaanxi, 710072, China
| | - Yuhang Wang
- The First Affiliated Hospital of Soochow University, Suzhou, China
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Suzhou, China
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
| | - Jiaqi Wei
- The First Affiliated Hospital of Soochow University, Suzhou, China
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Suzhou, China
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
| | - Jianhua Yu
- Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, 1500 East Duarte, Los Angeles, CA, 91010, USA.
- Hematologic Malignancies Research Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA.
| | - Xiaojin Wu
- The First Affiliated Hospital of Soochow University, Suzhou, China.
- National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Suzhou, China.
- Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
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Wang F, Cai G, Wang Y, Zhuang Q, Cai Z, Li Y, Gao S, Li F, Zhang C, Zhao B, Liu X. Circular RNA-based neoantigen vaccine for hepatocellular carcinoma immunotherapy. MedComm (Beijing) 2024; 5:e667. [PMID: 39081513 PMCID: PMC11286538 DOI: 10.1002/mco2.667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 05/29/2024] [Accepted: 06/10/2024] [Indexed: 08/02/2024] Open
Abstract
mRNA vaccines are regarded as a highly promising avenue for next-generation cancer therapy. Nevertheless, the intricacy of production, inherent instability, and low expression persistence of linear mRNA significantly restrict their extensive utilization. Circular RNAs (circRNAs) offer a novel solution to these limitations due to their efficient protein expression ability, which can be rapidly generated in vitro without the need for extra modifications. Here, we present a novel neoantigen vaccine based on circRNA that induces a potent anti-tumor immune response by expressing hepatocellular carcinoma-specific tumor neoantigens. By cyclizing linearRNA molecules, we were able to enhance the stability of RNA vaccines and form highly stable circRNA molecules with the capacity for sustained protein expression. We confirmed that neoantigen-encoded circRNA can promote dendritic cell (DC) activation and enhance DC-induced T-cell activation in vitro, thereby enhancing T-cell killing of tumor cells. Encapsulating neoantigen-encoded circRNA within lipid nanoparticles for in vivo expression has enabled the creation of a novel circRNA vaccine platform. This platform demonstrates superior tumor treatment and prevention in various murine tumor models, eliciting a robust T-cell immune response. Our circRNA neoantigen vaccine offers new options and application prospects for neoantigen immunotherapy in solid tumors.
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Affiliation(s)
- Fei Wang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian ProvinceMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouP. R. China
- Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic TumorsFuzhouP. R. China
- Mengchao Med‐X CenterFuzhou UniversityFuzhouP. R. China
| | - Guang Cai
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian ProvinceMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouP. R. China
- Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic TumorsFuzhouP. R. China
- Mengchao Med‐X CenterFuzhou UniversityFuzhouP. R. China
| | - Yingchao Wang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian ProvinceMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouP. R. China
- Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic TumorsFuzhouP. R. China
- Mengchao Med‐X CenterFuzhou UniversityFuzhouP. R. China
| | - Qiuyu Zhuang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian ProvinceMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouP. R. China
- Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic TumorsFuzhouP. R. China
- Mengchao Med‐X CenterFuzhou UniversityFuzhouP. R. China
| | - Zhixiong Cai
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian ProvinceMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouP. R. China
- Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic TumorsFuzhouP. R. China
- Mengchao Med‐X CenterFuzhou UniversityFuzhouP. R. China
| | - Yingying Li
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian ProvinceMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouP. R. China
- Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic TumorsFuzhouP. R. China
- Mengchao Med‐X CenterFuzhou UniversityFuzhouP. R. China
| | - Shaodong Gao
- School of Basic Medical SciencesFujian Medical UniversityFuzhouP. R. China
| | - Fang Li
- School of Basic Medical SciencesFujian Medical UniversityFuzhouP. R. China
| | - Cuilin Zhang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian ProvinceMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouP. R. China
- Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic TumorsFuzhouP. R. China
- Mengchao Med‐X CenterFuzhou UniversityFuzhouP. R. China
| | - Bixing Zhao
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian ProvinceMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouP. R. China
- Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic TumorsFuzhouP. R. China
- Mengchao Med‐X CenterFuzhou UniversityFuzhouP. R. China
| | - Xiaolong Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian ProvinceMengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouP. R. China
- Fujian Provincial Clinical Research Center for Hepatobiliary and Pancreatic TumorsFuzhouP. R. China
- Mengchao Med‐X CenterFuzhou UniversityFuzhouP. R. China
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28
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Li W, Wang C, Zhang Y, Lu Y. Lipid Nanocarrier-Based mRNA Therapy: Challenges and Promise for Clinical Transformation. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2310531. [PMID: 38287729 DOI: 10.1002/smll.202310531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 01/19/2024] [Indexed: 01/31/2024]
Abstract
Due to the outbreak of novel coronavirus pneumonia, messenger RNA (mRNA) technology has attracted heated attention. A specific, safe, and efficient mRNA delivery system is needed. Lipid nanocarriers have become attractive carriers for mRNA delivery due to their high delivery efficiency, few side effects, and easy modification to change their structures and functions. To achieve the desired biological effect, lipid nanocarriers must reach the designated location for effective drug delivery. Therefore, the effects of the composition of lipid nanocarriers on their key properties are briefly reviewed. In addition, the progress of smart drug delivery by changing the composition of lipid nanocarriers is summarized, and the importance of component design and structure is emphasized. Subsequently, this review summarizes the latest progress in lipid nanocarrier-based mRNA technology and provides corresponding strategies for its current challenges, putting forward valuable information for the future design of lipid nanocarriers and mRNA.
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Affiliation(s)
- Wenchao Li
- Department of Chemical Engineering, Tsinghua University, Beijing, 100084, China
- Key Laboratory of Industrial Biocatalysis, Ministry of Education, Tsinghua University, Beijing, 100084, China
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, 100029, China
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China
| | - Chen Wang
- Department of Chemical Engineering, Tsinghua University, Beijing, 100084, China
- Key Laboratory of Industrial Biocatalysis, Ministry of Education, Tsinghua University, Beijing, 100084, China
| | - Yifei Zhang
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, 100029, China
- Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China
| | - Yuan Lu
- Department of Chemical Engineering, Tsinghua University, Beijing, 100084, China
- Key Laboratory of Industrial Biocatalysis, Ministry of Education, Tsinghua University, Beijing, 100084, China
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29
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Zhang S, Yu J, Liu Y, Xiong B, Fang Y, Zhu Y, Li S, Sun L, Zhou B, Sun Y, Wang L, Yue W, Yin H, Xu H. Photosynthetic Bacteria-Hitchhiking 2D iMXene-mRNA Vaccine to Enable Photo-Immunogene Cancer Therapy. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2307225. [PMID: 38742454 PMCID: PMC11267280 DOI: 10.1002/advs.202307225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 02/29/2024] [Indexed: 05/16/2024]
Abstract
Therapeutic mRNA vaccines have become powerful therapeutic tools for severe diseases, including infectious diseases and malignant neoplasms. mRNA vaccines encoding tumor-associated antigens provide unprecedented hope for many immunotherapies that have hit the bottleneck. However, the application of mRNA vaccines is limited because of biological instability, innate immunogenicity, and ineffective delivery in vivo. This study aims to construct a novel mRNA vaccine delivery nanosystem to successfully co-deliver a tumor-associated antigen (TAA) encoded by the Wilms' tumor 1 (WT1) mRNA. In this system, named PSB@Nb1.33C/mRNA, photosynthetic bacteria (PSB) efficiently delivers the iMXene-WT1 mRNA to the core tumor region using photo-driven and hypoxia-driven properties. The excellent photothermal therapeutic (PTT) properties of PSB and 2D iMxene (Nb1.33C) trigger tumor immunogenic cell death, which boosts the release of the WT1 mRNA. The released WT1 mRNA is translated, presenting the TAA and amplifying immune effect in vivo. The designed therapeutic strategy demonstrates an excellent ability to inhibit distant tumors and counteract postsurgical lung metastasis. Thus, this study provides an innovative and effective paradigm for tumor immunotherapy, i.e., photo-immunogene cancer therapy, and establishes an efficient delivery platform for mRNA vaccines, thereby opening a new path for the wide application of mRNA vaccines.
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Affiliation(s)
- Shen Zhang
- Department of UltrasoundInstitute of Ultrasound in Medicine and EngineeringZhongshan HospitalFudan UniversityShanghai200032P. R. China
| | - Jifeng Yu
- Department of UltrasoundInstitute of Ultrasound in Medicine and EngineeringZhongshan HospitalFudan UniversityShanghai200032P. R. China
| | - Yunyun Liu
- Department of Medical UltrasoundCenter of Minimally Invasive Treatment for TumorShanghai Tenth People's HospitalUltrasound Research and Education InstituteClinical Research Center for Interventional MedicineSchool of MedicineTongji University. Shanghai 200072P. R. China
- Department of Medical UltrasoundShanghai Tenth People's HospitalNanjing Medical UniversityShanghai200072P. R. China
- Shanghai Engineering Research Center of Ultrasound Diagnosis and TreatmentShanghai200072P. R. China
| | - Bing Xiong
- Department of UltrasoundInstitute of Ultrasound in Medicine and EngineeringZhongshan HospitalFudan UniversityShanghai200032P. R. China
| | - Yan Fang
- Department of Medical UltrasoundCenter of Minimally Invasive Treatment for TumorShanghai Tenth People's HospitalUltrasound Research and Education InstituteClinical Research Center for Interventional MedicineSchool of MedicineTongji University. Shanghai 200072P. R. China
- Department of Medical UltrasoundShanghai Tenth People's HospitalNanjing Medical UniversityShanghai200072P. R. China
- Shanghai Engineering Research Center of Ultrasound Diagnosis and TreatmentShanghai200072P. R. China
| | - Yuli Zhu
- Department of UltrasoundInstitute of Ultrasound in Medicine and EngineeringZhongshan HospitalFudan UniversityShanghai200032P. R. China
| | - Shaoyue Li
- Department of Medical UltrasoundCenter of Minimally Invasive Treatment for TumorShanghai Tenth People's HospitalUltrasound Research and Education InstituteClinical Research Center for Interventional MedicineSchool of MedicineTongji University. Shanghai 200072P. R. China
- Department of Medical UltrasoundShanghai Tenth People's HospitalNanjing Medical UniversityShanghai200072P. R. China
- Shanghai Engineering Research Center of Ultrasound Diagnosis and TreatmentShanghai200072P. R. China
| | - Liping Sun
- Department of Medical UltrasoundCenter of Minimally Invasive Treatment for TumorShanghai Tenth People's HospitalUltrasound Research and Education InstituteClinical Research Center for Interventional MedicineSchool of MedicineTongji University. Shanghai 200072P. R. China
- Department of Medical UltrasoundShanghai Tenth People's HospitalNanjing Medical UniversityShanghai200072P. R. China
- Shanghai Engineering Research Center of Ultrasound Diagnosis and TreatmentShanghai200072P. R. China
| | - Boyang Zhou
- Department of UltrasoundInstitute of Ultrasound in Medicine and EngineeringZhongshan HospitalFudan UniversityShanghai200032P. R. China
| | - Yikang Sun
- Department of UltrasoundInstitute of Ultrasound in Medicine and EngineeringZhongshan HospitalFudan UniversityShanghai200032P. R. China
| | - Lifan Wang
- Department of UltrasoundInstitute of Ultrasound in Medicine and EngineeringZhongshan HospitalFudan UniversityShanghai200032P. R. China
| | - Wenwen Yue
- Department of Medical UltrasoundCenter of Minimally Invasive Treatment for TumorShanghai Tenth People's HospitalUltrasound Research and Education InstituteClinical Research Center for Interventional MedicineSchool of MedicineTongji University. Shanghai 200072P. R. China
- Department of Medical UltrasoundShanghai Tenth People's HospitalNanjing Medical UniversityShanghai200072P. R. China
- Shanghai Engineering Research Center of Ultrasound Diagnosis and TreatmentShanghai200072P. R. China
| | - Haohao Yin
- Department of UltrasoundInstitute of Ultrasound in Medicine and EngineeringZhongshan HospitalFudan UniversityShanghai200032P. R. China
| | - Huixiong Xu
- Department of UltrasoundInstitute of Ultrasound in Medicine and EngineeringZhongshan HospitalFudan UniversityShanghai200032P. R. China
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30
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Song J, Zhang Y, Zhou C, Zhan J, Cheng X, Huang H, Mao S, Zong Z. The dawn of a new Era: mRNA vaccines in colorectal cancer immunotherapy. Int Immunopharmacol 2024; 132:112037. [PMID: 38599100 DOI: 10.1016/j.intimp.2024.112037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 03/24/2024] [Accepted: 04/05/2024] [Indexed: 04/12/2024]
Abstract
Colorectal cancer (CRC) is a typical cancer that accounts for 10% of all new cancer cases annually and nearly 10% of all cancer deaths. Despite significant progress in current classical interventions for CRC, these traditional strategies could be invasive and with numerous adverse effects. The poor prognosis of CRC patients highlights the evident and pressing need for more efficient and targeted treatment. Novel strategies regarding mRNA vaccines for anti-tumor therapy have also been well-developed since the successful application for the prevention of COVID-19. mRNA vaccine technology won the 2023 Nobel Prize in Physiology or Medicine, signaling a new direction in human anti-cancer treatment: mRNA medicine. As a promising new immunotherapy in CRC and other multiple cancer treatments, the mRNA vaccine has higher specificity, better efficacy, and fewer side effects than traditional strategies. The present review outlines the basics of mRNA vaccines and their advantages over other vaccines and informs an available strategy for developing efficient mRNA vaccines for CRC precise treatment. In the future, more exploration of mRNA vaccines for CRC shall be attached, fostering innovation to address existing limitations.
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Affiliation(s)
- Jingjing Song
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No.1 MinDe Road, Nanchang 330006, Jiangxi, China; School of Ophthalmology and Optometry, Nanchang University, Nanchang 330006, Jiangxi, China
| | - Yujun Zhang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No.1 MinDe Road, Nanchang 330006, Jiangxi, China; Huankui Academy, Nanchang University, Nanchang 330006, Jiangxi, China
| | - Chulin Zhou
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No.1 MinDe Road, Nanchang 330006, Jiangxi, China; The Second Clinical Medical College, Nanchang University, Nanchang 330006, Jiangxi, China
| | - Jianhao Zhan
- Huankui Academy, Nanchang University, Nanchang 330006, Jiangxi, China
| | - Xifu Cheng
- School of Ophthalmology and Optometry, Nanchang University, Nanchang 330006, Jiangxi, China
| | - Haoyu Huang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No.1 MinDe Road, Nanchang 330006, Jiangxi, China
| | - Shengxun Mao
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No.1 MinDe Road, Nanchang 330006, Jiangxi, China.
| | - Zhen Zong
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, No.1 MinDe Road, Nanchang 330006, Jiangxi, China.
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31
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Lemmens M, Dorsheimer L, Zeller A, Dietz-Baum Y. Non-clinical safety assessment of novel drug modalities: Genome safety perspectives on viral-, nuclease- and nucleotide-based gene therapies. MUTATION RESEARCH. GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 2024; 896:503767. [PMID: 38821669 DOI: 10.1016/j.mrgentox.2024.503767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 04/08/2024] [Accepted: 05/13/2024] [Indexed: 06/02/2024]
Abstract
Gene therapies have emerged as promising treatments for various conditions including inherited diseases as well as cancer. Ensuring their safe clinical application requires the development of appropriate safety testing strategies. Several guidelines have been provided by health authorities to address these concerns. These guidelines state that non-clinical testing should be carried out on a case-by-case basis depending on the modality. This review focuses on the genome safety assessment of frequently used gene therapy modalities, namely Adeno Associated Viruses (AAVs), Lentiviruses, designer nucleases and mRNAs. Important safety considerations for these modalities, amongst others, are vector integrations into the patient genome (insertional mutagenesis) and off-target editing. Taking into account the constraints of in vivo studies, health authorities endorse the development of novel approach methodologies (NAMs), which are innovative in vitro strategies for genotoxicity testing. This review provides an overview of NAMs applied to viral and CRISPR/Cas9 safety, including next generation sequencing-based methods for integration site analysis and off-target editing. Additionally, NAMs to evaluate the oncogenicity risk arising from unwanted genomic modifications are discussed. Thus, a range of promising techniques are available to support the safe development of gene therapies. Thorough validation, comparisons and correlations with clinical outcomes are essential to identify the most reliable safety testing strategies. By providing a comprehensive overview of these NAMs, this review aims to contribute to a better understanding of the genome safety perspectives of gene therapies.
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Affiliation(s)
| | - Lena Dorsheimer
- Research and Development, Preclinical Safety, Sanofi, Industriepark Hoechst, Frankfurt am Main 65926, Germany.
| | - Andreas Zeller
- Pharmaceutical Sciences, pRED Innovation Center Basel, Hoffmann-La Roche Ltd, Basel 4070, Switzerland
| | - Yasmin Dietz-Baum
- Research and Development, Preclinical Safety, Sanofi, Industriepark Hoechst, Frankfurt am Main 65926, Germany
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Sarkar A, Dong G, Quaglia-Motta J, Sackett K. Flow-NMR as a Process-Monitoring Tool for mRNA IVT Reaction. J Pharm Sci 2024; 113:900-905. [PMID: 38008177 DOI: 10.1016/j.xphs.2023.11.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 11/08/2023] [Accepted: 11/21/2023] [Indexed: 11/28/2023]
Abstract
Messenger RNA (mRNA) based vaccines were instrumental in accelerating the end of the SARS-CoV-2 pandemic and are being aggressively developed as prophylaxes for a range of viral diseases. The swift adoption of mRNA-based therapeutics has also left open vast areas of opportunity for improving the development of mRNA-based drugs. One such area with immense potential focuses on the mRNA drug substance production, where mRNA is generated by a cell-free reaction called in vitro transcription (IVT). Process analytical technologies (PAT) are integral to the pharmaceutical industry and are necessary to facilitate agile process optimization and enhance process quality, control, and understanding. Due to the complexity and novelty inherent to the IVT reaction, there is a need for effective PAT that would provide in-depth, real-time insight into the reaction process to allow delivery of novel mRNA vaccines to patients faster in a more cost-effective way. Herein, we showcase the development of flow-nuclear magnetic resonance (flow-NMR) as a highly effective process-analytical tool for monitoring mRNA IVT reactions to support process development, optimization, and production.
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Affiliation(s)
- Aritra Sarkar
- Analytical Research and Development, Pfizer Research and Development, Eastern Point Road, Groton, CT 06340, United States of America.
| | - Guogang Dong
- Bioprocess Research and Development, Pfizer Research and Development, 1 Burtt Road, Andover, Massachusetts 01810, United States of America
| | - Jennifer Quaglia-Motta
- Bioprocess Research and Development, Pfizer Research and Development, 1 Burtt Road, Andover, Massachusetts 01810, United States of America
| | - Kelly Sackett
- Analytical Research and Development, Pfizer Research and Development, Eastern Point Road, Groton, CT 06340, United States of America.
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Wang J, Zhu H, Gan J, Liang G, Li L, Zhao Y. Engineered mRNA Delivery Systems for Biomedical Applications. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2308029. [PMID: 37805865 DOI: 10.1002/adma.202308029] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 10/05/2023] [Indexed: 10/09/2023]
Abstract
Messenger RNA (mRNA)-based therapeutic strategies have shown remarkable promise in preventing and treating a staggering range of diseases. Optimizing the structure and delivery system of engineered mRNA has greatly improved its stability, immunogenicity, and protein expression levels, which has led to a wider range of uses for mRNA therapeutics. Herein, a thorough analysis of the optimization strategies used in the structure of mRNA is first provided and delivery systems are described in great detail. Furthermore, the latest advancements in biomedical engineering for mRNA technology, including its applications in combatting infectious diseases, treating cancer, providing protein replacement therapy, conducting gene editing, and more, are summarized. Lastly, a perspective on forthcoming challenges and prospects concerning the advancement of mRNA therapeutics is offered. Despite these challenges, mRNA-based therapeutics remain promising, with the potential to revolutionize disease treatment and contribute to significant advancements in the biomedical field.
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Affiliation(s)
- Ji Wang
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Haofang Zhu
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Jingjing Gan
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Gaofeng Liang
- Institute of Organoids on Chips Translational Research, Henan Academy of Sciences, Zhengzhou, 450009, China
| | - Ling Li
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Yuanjin Zhao
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
- Institute of Organoids on Chips Translational Research, Henan Academy of Sciences, Zhengzhou, 450009, China
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Parhiz H, Atochina-Vasserman EN, Weissman D. mRNA-based therapeutics: looking beyond COVID-19 vaccines. Lancet 2024; 403:1192-1204. [PMID: 38461842 DOI: 10.1016/s0140-6736(23)02444-3] [Citation(s) in RCA: 64] [Impact Index Per Article: 64.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 07/06/2023] [Accepted: 10/30/2023] [Indexed: 03/12/2024]
Abstract
Recent advances in mRNA technology and its delivery have enabled mRNA-based therapeutics to enter a new era in medicine. The rapid, potent, and transient nature of mRNA-encoded proteins, without the need to enter the nucleus or the risk of genomic integration, makes them desirable tools for treatment of a range of diseases, from infectious diseases to cancer and monogenic disorders. The rapid pace and ease of mass-scale manufacturability of mRNA-based therapeutics supported the global response to the COVID-19 pandemic. Nonetheless, challenges remain with regards to mRNA stability, duration of expression, delivery efficiency, and targetability, to broaden the applicability of mRNA therapeutics beyond COVID-19 vaccines. By learning from the rapidly expanding preclinical and clinical studies, we can optimise the mRNA platform to meet the clinical needs of each disease. Here, we will summarise the recent advances in mRNA technology; its use in vaccines, immunotherapeutics, protein replacement therapy, and genomic editing; and its delivery to desired specific cell types and organs for development of a new generation of targeted mRNA-based therapeutics.
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Affiliation(s)
- Hamideh Parhiz
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | | | - Drew Weissman
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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Estapé Senti M, García Del Valle L, Schiffelers RM. mRNA delivery systems for cancer immunotherapy: Lipid nanoparticles and beyond. Adv Drug Deliv Rev 2024; 206:115190. [PMID: 38307296 DOI: 10.1016/j.addr.2024.115190] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 01/21/2024] [Accepted: 01/23/2024] [Indexed: 02/04/2024]
Abstract
mRNA-based vaccines are emerging as a promising alternative to standard cancer treatments and the conventional vaccines. Moreover, the FDA-approval of three nucleic acid based therapeutics (Onpattro, BNT162b2 and mRNA-1273) has further increased the interest and trust on this type of therapeutics. In order to achieve a significant therapeutic efficacy, the mRNA needs from a drug delivery system. In the last years, several delivery platforms have been explored, being the lipid nanoparticles (LNPs) the most well characterized and studied. A better understanding on how mRNA-based therapeutics operate (both the mRNA itself and the drug delivery system) will help to further improve their efficacy and safety. In this review, we will provide an overview of what mRNA cancer vaccines are and their mode of action and we will highlight the advantages and challenges of the different delivery platforms that are under investigation.
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Affiliation(s)
- Mariona Estapé Senti
- CDL Research, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands
| | - Lucía García Del Valle
- CDL Research, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands
| | - Raymond M Schiffelers
- CDL Research, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands.
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Gu X, Qi Y, El-Kebir M. DERNA Enables Pareto Optimal RNA Design. J Comput Biol 2024; 31:179-196. [PMID: 38416637 DOI: 10.1089/cmb.2023.0283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2024] Open
Abstract
The design of an RNA sequence v that encodes an input target protein sequence w is a crucial aspect of messenger RNA (mRNA) vaccine development. There are an exponential number of possible RNA sequences for a single target protein due to codon degeneracy. These potential RNA sequences can assume various secondary structure conformations, each with distinct minimum free energy (MFE), impacting thermodynamic stability and mRNA half-life. Furthermore, the presence of species-specific codon usage bias, quantified by the codon adaptation index (CAI), plays a vital role in translation efficiency. While earlier studies focused on optimizing either MFE or CAI, recent research has underscored the advantages of simultaneously optimizing both objectives. However, optimizing one objective comes at the expense of the other. In this work, we present the Pareto Optimal RNA Design problem, aiming to identify the set of Pareto optimal solutions for which no alternative solutions exist that exhibit better MFE and CAI values. Our algorithm DEsign RNA (DERNA) uses the weighted sum method to enumerate the Pareto front by optimizing convex combinations of both objectives. We use dynamic programming to solve each convex combination in O ( | w | 3 ) time and O ( | w | 2 ) space. Compared with a CDSfold, previous approach that only optimizes MFE, we show on a benchmark data set that DERNA obtains solutions with identical MFE but superior CAI. Moreover, we show that DERNA matches the performance in terms of solution quality of LinearDesign, a recent approach that similarly seeks to balance MFE and CAI. We conclude by demonstrating our method's potential for mRNA vaccine design for the SARS-CoV-2 spike protein.
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Affiliation(s)
- Xinyu Gu
- Department of Computer Science and University of Illinois Urbana-Champaign, Urbana, Illinois, USA
| | - Yuanyuan Qi
- Department of Computer Science and University of Illinois Urbana-Champaign, Urbana, Illinois, USA
| | - Mohammed El-Kebir
- Department of Computer Science and University of Illinois Urbana-Champaign, Urbana, Illinois, USA
- Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, Illinois, USA
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Shi Y, Zhen X, Zhang Y, Li Y, Koo S, Saiding Q, Kong N, Liu G, Chen W, Tao W. Chemically Modified Platforms for Better RNA Therapeutics. Chem Rev 2024; 124:929-1033. [PMID: 38284616 DOI: 10.1021/acs.chemrev.3c00611] [Citation(s) in RCA: 32] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2024]
Abstract
RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential in disease prevention and treatment. However, despite their remarkable achievements, these therapies encounter substantial challenges including low stability, susceptibility to degradation by nucleases, and a prominent negative charge, thereby hindering further development. Chemically modified platforms have emerged as a strategic innovation, focusing on precise alterations either on the RNA moieties or their associated delivery vectors. This comprehensive review delves into these platforms, underscoring their significance in augmenting the performance and translational prospects of RNA-based therapeutics. It encompasses an in-depth analysis of various chemically modified delivery platforms that have been instrumental in propelling RNA therapeutics toward clinical utility. Moreover, the review scrutinizes the rationale behind diverse chemical modification techniques aiming at optimizing the therapeutic efficacy of RNA molecules, thereby facilitating robust disease management. Recent empirical studies corroborating the efficacy enhancement of RNA therapeutics through chemical modifications are highlighted. Conclusively, we offer profound insights into the transformative impact of chemical modifications on RNA drugs and delineates prospective trajectories for their future development and clinical integration.
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Affiliation(s)
- Yesi Shi
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Xueyan Zhen
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
| | - Yiming Zhang
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
| | - Yongjiang Li
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
| | - Seyoung Koo
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
| | - Qimanguli Saiding
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
| | - Na Kong
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou 310058, China
| | - Gang Liu
- State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Wei Chen
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
- Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan
| | - Wei Tao
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
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Yang X, Yang C, Zhang S, Geng H, Zhu AX, Bernards R, Qin W, Fan J, Wang C, Gao Q. Precision treatment in advanced hepatocellular carcinoma. Cancer Cell 2024; 42:180-197. [PMID: 38350421 DOI: 10.1016/j.ccell.2024.01.007] [Citation(s) in RCA: 122] [Impact Index Per Article: 122.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 12/01/2023] [Accepted: 01/17/2024] [Indexed: 02/15/2024]
Abstract
The past decade has witnessed significant advances in the systemic treatment of advanced hepatocellular carcinoma (HCC). Nevertheless, the newly developed treatment strategies have not achieved universal success and HCC patients frequently exhibit therapeutic resistance to these therapies. Precision treatment represents a paradigm shift in cancer treatment in recent years. This approach utilizes the unique molecular characteristics of individual patient to personalize treatment modalities, aiming to maximize therapeutic efficacy while minimizing side effects. Although precision treatment has shown significant success in multiple cancer types, its application in HCC remains in its infancy. In this review, we discuss key aspects of precision treatment in HCC, including therapeutic biomarkers, molecular classifications, and the heterogeneity of the tumor microenvironment. We also propose future directions, ranging from revolutionizing current treatment methodologies to personalizing therapy through functional assays, which will accelerate the next phase of advancements in this area.
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Affiliation(s)
- Xupeng Yang
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Chen Yang
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Immune Regulation in Cancer Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Shu Zhang
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China
| | - Haigang Geng
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Andrew X Zhu
- I-Mab Biopharma, Shanghai, China; Jiahui International Cancer Center, Jiahui Health, Shanghai, China
| | - René Bernards
- Division of Molecular Carcinogenesis, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Wenxin Qin
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - Cun Wang
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Qiang Gao
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
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39
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Liu M, Zhang R, Huang H, Liu P, Zhao X, Wu H, He Y, Xu R, Qin X, Cheng Z, Liu H, Ergonul O, Can F, Ouyang D, Wang Z, Pang Z, Liu F. Erythrocyte-Leveraged Oncolytic Virotherapy (ELeOVt): Oncolytic Virus Assembly on Erythrocyte Surface to Combat Pulmonary Metastasis and Alleviate Side Effects. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2303907. [PMID: 37997186 PMCID: PMC10837356 DOI: 10.1002/advs.202303907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 10/24/2023] [Indexed: 11/25/2023]
Abstract
Despite being a new promising tool for cancer therapy, intravenous delivery of oncolytic viruses (OVs) is greatly limited by poor tumor targeting, rapid clearance in the blood, severe organ toxicity, and cytokine release syndrome. Herein, a simple and efficient strategy of erythrocyte-leveraged oncolytic virotherapy (ELeOVt) is reported, which for the first time assembled OVs on the surface of erythrocytes with up to near 100% efficiency and allowed targeted delivery of OVs to the lung after intravenous injection to achieve excellent treatment of pulmonary metastases while greatly improving the biocompatibility of OVs as a drug. Polyethyleneimine (PEI) as a bridge to assemble OVs on erythrocytes also played an important role in promoting the transfection of OVs. It is found that ELeOVt approach significantly prolonged the circulation time of OVs and increased the OVs distribution in the lung by more than tenfold, thereby significantly improving the treatment of lung metastases while reducing organ and systemic toxicity. Taken together, these findings suggest that the ELeOVt provides a biocompatible, efficient, and widely available approach to empower OVs to combat lung metastasis.
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Affiliation(s)
- Mingyang Liu
- Department of Surgical Oncology and General SurgeryThe First Hospital of China Medical University155 North Nanjing Street, Heping DistrictShenyang110001China
- Department of PharmaceuticsSchool of PharmacyFudan University and Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai201203China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal TumorsChina Medical UniversityMinistry of Education155 North Nanjing Street, Heping DistrictShenyang110001China
| | - Ruizhe Zhang
- Department of Surgical Oncology and General SurgeryThe First Hospital of China Medical University155 North Nanjing Street, Heping DistrictShenyang110001China
- Department of PharmaceuticsSchool of PharmacyFudan University and Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai201203China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal TumorsChina Medical UniversityMinistry of Education155 North Nanjing Street, Heping DistrictShenyang110001China
| | - Hanwei Huang
- Department of Surgical Oncology and General SurgeryThe First Hospital of China Medical University155 North Nanjing Street, Heping DistrictShenyang110001China
- Department of PharmaceuticsSchool of PharmacyFudan University and Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai201203China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal TumorsChina Medical UniversityMinistry of Education155 North Nanjing Street, Heping DistrictShenyang110001China
| | - Pengfei Liu
- Department of Surgical Oncology and General SurgeryThe First Hospital of China Medical University155 North Nanjing Street, Heping DistrictShenyang110001China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal TumorsChina Medical UniversityMinistry of Education155 North Nanjing Street, Heping DistrictShenyang110001China
| | - Xu Zhao
- Department of Surgical Oncology and General SurgeryThe First Hospital of China Medical University155 North Nanjing Street, Heping DistrictShenyang110001China
- Department of PharmaceuticsSchool of PharmacyFudan University and Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai201203China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal TumorsChina Medical UniversityMinistry of Education155 North Nanjing Street, Heping DistrictShenyang110001China
| | - Hu Wu
- Department of Surgical Oncology and General SurgeryThe First Hospital of China Medical University155 North Nanjing Street, Heping DistrictShenyang110001China
- Department of PharmaceuticsSchool of PharmacyFudan University and Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai201203China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal TumorsChina Medical UniversityMinistry of Education155 North Nanjing Street, Heping DistrictShenyang110001China
| | - Ying He
- Department of PharmaceuticsSchool of PharmacyFudan University and Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai201203China
| | - Ruizhe Xu
- Department of PharmaceuticsSchool of PharmacyFudan University and Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai201203China
| | - Xifeng Qin
- Department of PharmaceuticsSchool of PharmacyFudan University and Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai201203China
| | - Zhenguo Cheng
- Sino‐British Research Centre for Molecular OncologyNational Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhou450052China
| | - Hongyu Liu
- Department of Surgical Oncology and General SurgeryThe First Hospital of China Medical University155 North Nanjing Street, Heping DistrictShenyang110001China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal TumorsChina Medical UniversityMinistry of Education155 North Nanjing Street, Heping DistrictShenyang110001China
| | - Onder Ergonul
- Koç University Iş Bank Center for Infectious Diseases (KUISCID)Koç University School of Medicine and American HospitalIstanbul34010Turkey
| | - Füsun Can
- Koç University Iş Bank Center for Infectious Diseases (KUISCID)Koç University School of Medicine and American HospitalIstanbul34010Turkey
| | - Defang Ouyang
- State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical Sciences (ICMS)University of MacauMacau999078China
| | - Zhenning Wang
- Department of Surgical Oncology and General SurgeryThe First Hospital of China Medical University155 North Nanjing Street, Heping DistrictShenyang110001China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal TumorsChina Medical UniversityMinistry of Education155 North Nanjing Street, Heping DistrictShenyang110001China
| | - Zhiqing Pang
- Department of PharmaceuticsSchool of PharmacyFudan University and Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai201203China
| | - Funan Liu
- Department of Surgical Oncology and General SurgeryThe First Hospital of China Medical University155 North Nanjing Street, Heping DistrictShenyang110001China
- Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal TumorsChina Medical UniversityMinistry of Education155 North Nanjing Street, Heping DistrictShenyang110001China
- Phase I Clinical Trials CenterThe First HospitalChina Medical University518 North Chuangxin Road, Baita Street, Hunnan DistrictShenyangLiaoning110102China
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40
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Bui NL, Chu DT. An introduction to RNA therapeutics and their potentials. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2024; 203:1-12. [PMID: 38359993 DOI: 10.1016/bs.pmbts.2023.12.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/17/2024]
Abstract
RNA therapeutics is a biological term regarding the usage of RNA-based molecules for medical purposes. Thanks to the success of mRNA-vaccine production against COVID-19, RNA therapeutics has gained more and more attention and investigation from worldwide scientists. It is considered as one of the promising alternatives for conventional drugs. In this first chapter, we presented an overview of the history and perspectives of RNA therapeutics' development. This chapter also explained the underlying mechanisms of different RNA-based molecules, including antisense oligonucleotide, interfering RNA (iRNA), aptamer, and mRNA, from degrading mRNA to inactivating targeted protein. Although there are many advantages of RNA therapeutics, its challenges in designing RNA chemical structure and the delivery vehicle need to be discussed. We described advanced technologies in the development of drug delivery systems that are positively correlated to the efficacy of the drug. Our aim is to provide a general background of RNA therapeutics to the audience before introducing plenty of more detailed parts, including clinical applications in certain diseases in the following chapters of the "RNA therapeutics" book.
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Affiliation(s)
- Nhat-Le Bui
- Center for Biomedicine and Community Health, International School, Vietnam National University, Hanoi, Vietnam; Faculty of Applied Sciences, International School, Vietnam National University, Hanoi, Vietnam
| | - Dinh-Toi Chu
- Center for Biomedicine and Community Health, International School, Vietnam National University, Hanoi, Vietnam; Faculty of Applied Sciences, International School, Vietnam National University, Hanoi, Vietnam.
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41
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Nguyen MN, Than VT. RNA therapeutics in cancer treatment. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2024; 203:197-223. [PMID: 38359999 DOI: 10.1016/bs.pmbts.2024.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/17/2024]
Abstract
RNA therapeutics are a class of drugs that use RNA molecules to treat diseases, including cancer. RNA therapeutics work by targeting specific genes or proteins involved in the disease process, with the aim of blocking or altering their activity to ultimately halt or reverse the disease progression. The use of RNA therapeutics in cancer treatment has shown great potential, as they offer the ability to specifically target cancer cells while leaving healthy cells intact. This is in contrast to traditional chemotherapy and radiation treatments, which can damage healthy cells and cause unpleasant side effects. The field of RNA therapeutics is rapidly advancing, with several types of RNA molecules being developed for cancer treatment, including small interfering RNA, microRNA, mRNA, and RNA aptamers. Each type of RNA molecule has unique properties and mechanisms of action, allowing for targeted and personalized cancer treatments. In this chapter, we will explore the different types of RNA therapeutics used in cancer treatment, their mechanisms of action, and their potential applications in treating different types of cancer. We will also discuss the challenges and opportunities in the development and research of RNA therapeutics for cancer, as well as the future outlook for this promising field.
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Affiliation(s)
- Minh Nam Nguyen
- Department of Biomedical Engineering, School of Medicine, Vietnam National University Ho Chi Minh City (VNU-HCM), Ho Chi Minh City, Vietnam; Research Center for Genetics and Reproductive Health (CGRH), School of Medicine, National University HCMC, Ho Chi Minh City, Vietnam.
| | - Van Thai Than
- Faculty of Applied Sciences, International School, Vietnam National University, Hanoi, Vietnam
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42
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Malla R, Srilatha M, Farran B, Nagaraju GP. mRNA vaccines and their delivery strategies: A journey from infectious diseases to cancer. Mol Ther 2024; 32:13-31. [PMID: 37919901 PMCID: PMC10787123 DOI: 10.1016/j.ymthe.2023.10.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 10/31/2023] [Accepted: 10/31/2023] [Indexed: 11/04/2023] Open
Abstract
mRNA vaccines have evolved as promising cancer therapies. These vaccines can encode tumor-allied antigens, thus enabling personalized treatment approaches. They can also target cancer-specific mutations and overcome immune evasion mechanisms. They manipulate the body's cellular functions to produce antigens, elicit immune responses, and suppress tumors by overcoming limitations associated with specific histocompatibility leukocyte antigen molecules. However, successfully delivering mRNA into target cells destroys a crucial challenge. Viral and nonviral vectors (lipid nanoparticles and cationic liposomes) have shown great capacity in protecting mRNA from deterioration and assisting in cellular uptake. Cell-penetrating peptides, hydrogels, polymer-based nanoparticles, and dendrimers have been investigated to increase the delivery efficacy and immunogenicity of mRNA. This comprehensive review explores the landscape of mRNA vaccines and their delivery platforms for cancer, addressing design considerations, diverse delivery strategies, and recent advancements. Overall, this review contributes to the progress of mRNA vaccines as an innovative strategy for effective cancer treatment.
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Affiliation(s)
- RamaRao Malla
- Cancer Biology Lab, Department of Biochemistry and Bioinformatics, GITAM School of Science, GITAM (Deemed to be University), Visakhapatnam 530045, AP, India
| | - Mundla Srilatha
- Department of Biotechnology, Sri Venkateswara University, Tirupati 517502, AP, India
| | - Batoul Farran
- Department of Oncology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Ganji Purnachandra Nagaraju
- Department of Hematology and Oncology, Heersink School of Medicine, University of Alabama, Birmingham, AL 35233, USA.
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43
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Qu Y, Xu J, Zhang T, Chen Q, Sun T, Jiang C. Advanced nano-based strategies for mRNA tumor vaccine. Acta Pharm Sin B 2024; 14:170-189. [PMID: 38239240 PMCID: PMC10792970 DOI: 10.1016/j.apsb.2023.07.025] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 07/02/2023] [Accepted: 07/18/2023] [Indexed: 01/22/2024] Open
Abstract
Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune responses. Along with the technological breakthroughs in genetic engineering and delivery systems, messenger ribonucleic acid (mRNA) technology has achieved unprecedented development and application over the last few years, especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic, which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in vaccines. However, unlike infectious disease vaccines, which mainly induce humoral immunity, tumor vaccines also need to activate potent cellular immunity to control tumor growth, which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells (APCs). Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges, as well as future considerations of mRNA tumor vaccines and their delivery systems.
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Affiliation(s)
| | | | | | - Qinjun Chen
- Key Laboratory of Smart Drug Delivery (Ministry of Education), Minhang Hospital, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China
| | - Tao Sun
- Key Laboratory of Smart Drug Delivery (Ministry of Education), Minhang Hospital, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China
| | - Chen Jiang
- Key Laboratory of Smart Drug Delivery (Ministry of Education), Minhang Hospital, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China
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44
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Chen W, Zhu Y, He J, Sun X. Path towards mRNA delivery for cancer immunotherapy from bench to bedside. Theranostics 2024; 14:96-115. [PMID: 38164145 PMCID: PMC10750210 DOI: 10.7150/thno.89247] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 10/11/2023] [Indexed: 01/03/2024] Open
Abstract
Messenger RNA (mRNA) has emerged as a promising therapeutic agent for the prevention and treatment of various diseases. mRNA vaccines, in particular, offer an alternative approach to conventional vaccines, boasting high potency, rapid development capabilities, cost-effectiveness, and safe administration. However, the clinical application of mRNA vaccines is hindered by the challenges of mRNA instability and inefficient in vivo delivery. In recent times, remarkable technological advancements have emerged to address these challenges, utilizing two main approaches: ex vivo transfection of dendritic cells (DCs) with mRNA and direct injection of mRNA-based therapeutics, either with or without a carrier. This review offers a comprehensive overview of major non-viral vectors employed for mRNA vaccine delivery. It showcases notable preclinical and clinical studies in the field of cancer immunotherapy and discusses important considerations for advancing these promising vaccine platforms for broader therapeutic applications. Additionally, we provide insights into future possibilities and the remaining challenges in mRNA delivery technology, emphasizing the significance of ongoing research in mRNA-based therapeutics.
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Affiliation(s)
- Wenfei Chen
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
| | - Yining Zhu
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
- Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA
| | - Jinhan He
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Xun Sun
- Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
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45
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Li X, Qi J, Wang J, Hu W, Zhou W, Wang Y, Li T. Nanoparticle technology for mRNA: Delivery strategy, clinical application and developmental landscape. Theranostics 2024; 14:738-760. [PMID: 38169577 PMCID: PMC10758055 DOI: 10.7150/thno.84291] [Citation(s) in RCA: 26] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 11/28/2023] [Indexed: 01/05/2024] Open
Abstract
The mRNA vaccine, a groundbreaking advancement in the field of immunology, has garnered international recognition by being awarded the prestigious Nobel Prize, which has emerged as a promising prophylactic and therapeutic modality for various diseases, especially in cancer, rare disease, and infectious disease such as COVID-19, wherein successful mRNA treatment can be achieved by improving the stability of mRNA and introducing a safe and effective delivery system. Nanotechnology-based delivery systems, such as lipid nanoparticles, lipoplexes, polyplexes, lipid-polymer hybrid nanoparticles and others, have attracted great interest and have been explored for mRNA delivery. Nanoscale platforms can protect mRNA from extracellular degradation while promoting endosome escape after endocytosis, hence improving the efficacy. This review provides an overview of diverse nanoplatforms utilized for mRNA delivery in preclinical and clinical stages, including formulation, preparation process, transfection efficiency, and administration route. Furthermore, the market situation and prospects of mRNA vaccines are discussed here.
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Affiliation(s)
- Xiang Li
- Formulation and Process Development (FPD), WuXi Biologics, 291 Fucheng Road, Hangzhou, 311106, China
| | - Jing Qi
- Formulation and Process Development (FPD), WuXi Biologics, 291 Fucheng Road, Hangzhou, 311106, China
| | - Juan Wang
- Formulation and Process Development (FPD), WuXi Biologics, 291 Fucheng Road, Hangzhou, 311106, China
| | - Weiwei Hu
- WuXi Biologics, 291 Fucheng Road, Hangzhou, 311106, China
| | - Weichang Zhou
- WuXi Biologics, Waigaoqiao Free Trade Zone, Shanghai, 200131, China
| | - Yi Wang
- Formulation and Process Development (FPD), WuXi Biologics, 291 Fucheng Road, Hangzhou, 311106, China
| | - Tao Li
- Formulation and Process Development (FPD), WuXi Biologics, 291 Fucheng Road, Hangzhou, 311106, China
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46
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Fan T, Zhang M, Yang J, Zhu Z, Cao W, Dong C. Therapeutic cancer vaccines: advancements, challenges, and prospects. Signal Transduct Target Ther 2023; 8:450. [PMID: 38086815 PMCID: PMC10716479 DOI: 10.1038/s41392-023-01674-3] [Citation(s) in RCA: 167] [Impact Index Per Article: 83.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Revised: 09/08/2023] [Accepted: 09/19/2023] [Indexed: 12/18/2023] Open
Abstract
With the development and regulatory approval of immune checkpoint inhibitors and adoptive cell therapies, cancer immunotherapy has undergone a profound transformation over the past decades. Recently, therapeutic cancer vaccines have shown promise by eliciting de novo T cell responses targeting tumor antigens, including tumor-associated antigens and tumor-specific antigens. The objective was to amplify and diversify the intrinsic repertoire of tumor-specific T cells. However, the complete realization of these capabilities remains an ongoing pursuit. Therefore, we provide an overview of the current landscape of cancer vaccines in this review. The range of antigen selection, antigen delivery systems development the strategic nuances underlying effective antigen presentation have pioneered cancer vaccine design. Furthermore, this review addresses the current status of clinical trials and discusses their strategies, focusing on tumor-specific immunogenicity and anti-tumor efficacy assessment. However, current clinical attempts toward developing cancer vaccines have not yielded breakthrough clinical outcomes due to significant challenges, including tumor immune microenvironment suppression, optimal candidate identification, immune response evaluation, and vaccine manufacturing acceleration. Therefore, the field is poised to overcome hurdles and improve patient outcomes in the future by acknowledging these clinical complexities and persistently striving to surmount inherent constraints.
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Affiliation(s)
- Ting Fan
- Department of Oncology, East Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China
| | - Mingna Zhang
- Postgraduate Training Base, Shanghai East Hospital, Jinzhou Medical University, Shanghai, 200120, China
| | - Jingxian Yang
- Department of Oncology, East Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China
| | - Zhounan Zhu
- Department of Oncology, East Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China
| | - Wanlu Cao
- Department of Oncology, East Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China.
| | - Chunyan Dong
- Department of Oncology, East Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China.
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Zhao G, Bu G, Liu G, Kong X, Sun C, Li Z, Dai D, Sun H, Kang Y, Feng G, Zhong Q, Zeng M. mRNA-based Vaccines Targeting the T-cell Epitope-rich Domain of Epstein Barr Virus Latent Proteins Elicit Robust Anti-Tumor Immunity in Mice. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2302116. [PMID: 37890462 PMCID: PMC10724410 DOI: 10.1002/advs.202302116] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 09/04/2023] [Indexed: 10/29/2023]
Abstract
Epstein-Barr virus (EBV) is associated with various malignancies and infects >90% of the global population. EBV latent proteins are expressed in numerous EBV-associated cancers and contribute to carcinogenesis, making them critical therapeutic targets for these cancers. Thus, this study aims to develop mRNA-based therapeutic vaccines that express the T-cell-epitope-rich domain of truncated latent proteins of EBV, including truncatedlatent membrane protein 2A (Trunc-LMP2A), truncated EBV nuclear antigen 1 (Trunc-EBNA1), and Trunc-EBNA3A. The vaccines effectively activate both cellular and humoral immunity in mice and show promising results in suppressing tumor progression and improving survival time in tumor-bearing mice. Furthermore, it is observed that the truncated forms of the antigens, Trunc-LMP2A, Trunc-EBNA1, and Trunc-EBNA3A, are more effective than full-length antigens in activating antigen-specific immune responses. In summary, the findings demonstrate the effectiveness of mRNA-based therapeutic vaccines targeting the T-cell-epitope-rich domain of EBV latent proteins and providing new treatment options for EBV-associated cancers.
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Affiliation(s)
- Ge‐Xin Zhao
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer. MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma, Diagnosis, and TherapySun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Guo‐Long Bu
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer. MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma, Diagnosis, and TherapySun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Gang‐Feng Liu
- Department of Head and Neck Surgery Section IIThe Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Hospital519 Kunzhou RoadKunming650118China
| | - Xiang‐Wei Kong
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer. MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma, Diagnosis, and TherapySun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Cong Sun
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer. MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma, Diagnosis, and TherapySun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Zi‐Qian Li
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer. MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma, Diagnosis, and TherapySun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Dan‐Ling Dai
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer. MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma, Diagnosis, and TherapySun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Hai‐Xia Sun
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer. MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma, Diagnosis, and TherapySun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Yin‐Feng Kang
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer. MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma, Diagnosis, and TherapySun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Guo‐Kai Feng
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer. MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma, Diagnosis, and TherapySun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Qian Zhong
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer. MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma, Diagnosis, and TherapySun Yat‐sen University Cancer CenterGuangzhou510060China
| | - Mu‐Sheng Zeng
- State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer. MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma, Diagnosis, and TherapySun Yat‐sen University Cancer CenterGuangzhou510060China
- Guangdong‐Hong Kong Joint Laboratory for RNA MedicineSun Yat‐sen University Cancer CenterGuangzhou510060China
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Verma C, Pawar VA, Srivastava S, Tyagi A, Kaushik G, Shukla SK, Kumar V. Cancer Vaccines in the Immunotherapy Era: Promise and Potential. Vaccines (Basel) 2023; 11:1783. [PMID: 38140187 PMCID: PMC10747700 DOI: 10.3390/vaccines11121783] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/15/2023] [Accepted: 11/25/2023] [Indexed: 12/24/2023] Open
Abstract
Therapeutic vaccines are a promising alternative for active immunotherapy for different types of cancers. Therapeutic cancer vaccines aim to prevent immune system responses that are not targeted at the tumors only, but also boost the anti-tumor immunity and promote regression or eradication of the malignancy without, or with minimal, adverse events. Clinical trial data have pushed the development of cancer vaccines forward, and the US Food and Drug Administration authorized the first therapeutic cancer vaccine. In the present review, we discuss the various types of cancer vaccines and different approaches for the development of therapeutic cancer vaccines, along with the current state of knowledge and future prospects. We also discuss how tumor-induced immune suppression limits the effectiveness of therapeutic vaccinations, and strategies to overcome this barrier to design efficacious, long-lasting anti-tumor immune responses in the generation of vaccines.
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Affiliation(s)
- Chaitenya Verma
- Department of Pathology, Wexner Medical Center, Ohio State University, Columbus, OH 43210, USA;
| | | | - Shivani Srivastava
- Department of Pathology, School of Medicine, Yale University, New Haven, CT 06510, USA;
| | - Anuradha Tyagi
- Department of cBRN, Institute of Nuclear Medicine and Allied Science, Delhi 110054, India;
| | - Gaurav Kaushik
- School of Allied Health Sciences, Sharda University, Greater Noida 201310, India;
| | - Surendra Kumar Shukla
- Department of Oncology Science, OU Health Stephenson Cancer Center, Oklahoma City, OK 73104, USA
| | - Vinay Kumar
- Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43201, USA
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Wei Y, Zheng L, Yang X, Luo Y, Yi C, Gou H. Identification of Immune Subtypes and Candidate mRNA Vaccine Antigens in Small Cell Lung Cancer. Oncologist 2023; 28:e1052-e1064. [PMID: 37399175 PMCID: PMC10628581 DOI: 10.1093/oncolo/oyad193] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 06/12/2023] [Indexed: 07/05/2023] Open
Abstract
BACKGROUND Immune checkpoint inhibitors (ICIs) have demonstrated promising outcomes in small cell lung cancer (SCLC), but not all patients benefit from it. Thus, developing precise treatments for SCLC is a particularly urgent need. In our study, we constructed a novel phenotype for SCLC based on immune signatures. METHODS We clustered patients with SCLC hierarchically in 3 publicly available datasets according to the immune signatures. ESTIMATE and CIBERSORT algorithm were used to evaluate the components of the tumor microenvironment. Moreover, we identified potential mRNA vaccine antigens for patients with SCLC, and qRT-PCR were performed to detect the gene expression. RESULTS We identified 2 SCLC subtypes and named Immunity High (Immunity_H) and Immunity Low (Immunity_L). Meanwhile, we obtained generally consistent results by analyzing different datasets, suggesting that this classification was reliable. Immunity_H contained the higher number of immune cells and a better prognosis compared to Immunity_L. Gene-set enrichment analysis revealed that several immune-related pathways such as cytokine-cytokine receptor interaction, programmed cell death-Ligand 1 expression and programmed cell death-1 checkpoint pathway in cancer were hyperactivated in the Immunity_H. However, most of the pathways enriched in the Immunity_L were not associated with immunity. Furthermore, we identified 5 potential mRNA vaccine antigens of SCLC (NEK2, NOL4, RALYL, SH3GL2, and ZIC2), and they were expressed higher in Immunity_L, it indicated that Immunity_L maybe more suitable for tumor vaccine development. CONCLUSIONS SCLC can be divided into Immunity_H and Immunity_L subtypes. Immunity_H may be more suitable for treatment with ICIs. NEK2, NOL4, RALYL, SH3GL2, and ZIC2 may be act as potential antigens for SCLC.
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Affiliation(s)
- Yuanfeng Wei
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Lingnan Zheng
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Xi Yang
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Yong Luo
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Cheng Yi
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Hongfeng Gou
- Gastric Cancer Center, Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
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50
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Liu X, Huang P, Yang R, Deng H. mRNA Cancer Vaccines: Construction and Boosting Strategies. ACS NANO 2023; 17:19550-19580. [PMID: 37819640 DOI: 10.1021/acsnano.3c05635] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/13/2023]
Abstract
In late 2020, the U.S. Food and Drug Administration (FDA) approved a lipid-based mRNA vaccine for the prevention of COVID-19, which has pushed this field to be more closely studied and motivated researchers to delve deeper into mRNA therapeutics. To date, the research on mRNA cancer vaccines has been developed rapidly, and substantial hopeful therapeutic results have been achieved against various solid tumors in clinical trials. In this review, we first introduce three main components of mRNA cancer vaccines, including mRNA antigens, adjuvants, and delivery vectors. Engineering these components can optimize the therapeutic effects of mRNA cancer vaccines. For instance, appropriate modification of mRNA structure can alleviate the poor stability and innate immunogenicity of mRNA, and the use of mRNA delivery vectors can address the issues of low delivery efficiency in vivo. Second, we emphatically discuss some strategies to further improve the efficacy of mRNA cancer vaccines, namely modulating the immunosuppressive tumor environment, optimizing administration routes, achieving targeting delivery to intended tissues or organs, and employing combination therapy. These strategies can strengthen the tumor inhibitory ability of mRNA cancer vaccines and increase the possibility of tumor elimination. Finally, we point out some challenges in the clinical practice of mRNA cancer vaccines and offer our perspectives on future developments in this rapidly evolving field. It is anticipated that mRNA cancer vaccines will be rapidly developed for clinical cancer therapy in the near future.
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Affiliation(s)
- Xiaoqing Liu
- School of Advanced Materials and Nanotechnology, Xidian University, Xi'an 710126 China
- Ministry of Education, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Xi'an, Shaanxi 710126, China
- International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710126, China
| | - Pei Huang
- Ministry of Education, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Xi'an, Shaanxi 710126, China
- International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710126, China
- Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore 119074, Singapore
| | - Rusen Yang
- School of Advanced Materials and Nanotechnology, Xidian University, Xi'an 710126 China
| | - Hongzhang Deng
- Ministry of Education, School of Life Science and Technology, Xidian University & Engineering Research Center of Molecular and Neuro Imaging, Xi'an, Shaanxi 710126, China
- International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment & Xi'an Key Laboratory of Intelligent Sensing and Regulation of trans-Scale Life Information, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710126, China
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