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Liu T, Yao W, Sun W, Yuan Y, Liu C, Liu X, Wang X, Jiang H. Components, Formulations, Deliveries, and Combinations of Tumor Vaccines. ACS NANO 2024; 18:18801-18833. [PMID: 38979917 DOI: 10.1021/acsnano.4c05065] [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: 07/10/2024]
Abstract
Tumor vaccines, an important part of immunotherapy, prevent cancer or kill existing tumor cells by activating or restoring the body's own immune system. Currently, various formulations of tumor vaccines have been developed, including cell vaccines, tumor cell membrane vaccines, tumor DNA vaccines, tumor mRNA vaccines, tumor polypeptide vaccines, virus-vectored tumor vaccines, and tumor-in-situ vaccines. There are also multiple delivery systems for tumor vaccines, such as liposomes, cell membrane vesicles, viruses, exosomes, and emulsions. In addition, to decrease the risk of tumor immune escape and immune tolerance that may exist with a single tumor vaccine, combination therapy of tumor vaccines with radiotherapy, chemotherapy, immune checkpoint inhibitors, cytokines, CAR-T therapy, or photoimmunotherapy is an effective strategy. Given the critical role of tumor vaccines in immunotherapy, here, we look back to the history of tumor vaccines, and we discuss the antigens, adjuvants, formulations, delivery systems, mechanisms, combination therapy, and future directions of tumor vaccines.
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Affiliation(s)
- Tengfei Liu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China
| | - Wenyan Yao
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China
| | - Wenyu Sun
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China
| | - Yihan Yuan
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China
| | - Chen Liu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China
| | - Xiaohui Liu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China
| | - Xuemei Wang
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China
| | - Hui Jiang
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China
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Xu Y, Guo Y, Lu C, Yu L, Fang C, Li C. Polygonatum sibiricum Polysaccharide Inhibited Liver Cancer in a Simulated Tumor Microenvironment by Eliminating TLR4/STAT3 Pathway. Biol Pharm Bull 2023; 46:1249-1259. [PMID: 37661404 DOI: 10.1248/bpb.b23-00198] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
Liver cancer is one of the most aggressive tumors and one of the most common malignant tumors which seriously threatens human health. Traditional Chinese medicine (TCM) was reported to resist the proliferation and metastasis of liver cancer cells. In this study, we aimed to explore the potential anti-cancer effect of Polygonatum sibiricum polysaccharide (PSP) on the tumor immune microenvironment in liver cancer cells. HepG2 and Hep3B cells were pretreated in the absence or the presence of PSP (20, 50, 100 µg/mL) for a period of 24 h. Subsequently, dendritic cells (DCs) were co-cultured with HepG2 and Hep3B cell supernatant to investigate the effect of PSP on the tumor microenvironment. The results showed that PSP dose-dependently inhibited proliferation and promoted apoptosis of HepG2 and Hep3B cells. Meanwhile, PSP dose-dependently inhibited migration, invasion, and epithelial-to-mesenchymal transition (EMT) of liver cancer cells. In addition, PSP dose-dependently induced inflammatory response of DCs, characterized by increases of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in DCs. Mechanically, PSP dose-dependently reduced the activation of the Toll-like receptor 4 (TLR4)/Signal transducer and activator of transcription 3 (STAT3) and noncanonical nuclear factor-kappa B (NF-κB) signaling pathways. TLR4 agonist lipopolysaccharide (LPS) reversed the anti-oncogenic effects of PSP in liver cancer cells. Taken together, PSP inhibited liver cancer in a simulated tumor microenvironment by eliminating TLR4/STAT3 pathway. PSP promises an important and useful alternative to liver cancer treatment.
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Affiliation(s)
- Yunke Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University
| | - Yong Guo
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University
| | - Changyou Lu
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University
| | - Linlin Yu
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University
| | - Chao Fang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University
| | - Chuntao Li
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University
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Zhang Z, Ji W, Huang J, Zhang Y, Zhou Y, Zhang J, Dong Y, Yuan T, Yang Q, Ding X, Tang L, Li H, Yin J, Wang Y, Ji T, Fei J, Zhang B, Chen P, Hu H. Characterization of the tumour microenvironment phenotypes in malignant tissues and pleural effusion from advanced osteoblastic osteosarcoma patients. Clin Transl Med 2022; 12:e1072. [PMID: 36305631 PMCID: PMC9615475 DOI: 10.1002/ctm2.1072] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 09/16/2022] [Accepted: 09/23/2022] [Indexed: 01/28/2023] Open
Abstract
PURPOSE Malignant pleural effusion (MPE) is an adverse prognostic factor in patients with osteoblastic osteosarcoma; however, the cellular contexts of MPE are largely unknown. EXPERIMENTAL DESIGN We performed single-cell RNA-sequencing (scRNA-seq) on 27 260 cells from seven MPE samples and 91 186 cells from eight osteosarcoma tissues, including one recurrent, one lung metastasis and six primary tumour (PT) samples, to characterize their tumour microenvironment. RESULTS Thirteen main cell groups were identified in osteosarcoma tumour and MPE samples. Immune cells dominate the cellular contexts in MPE with more T/NK cells and less osteoclasts compared to PT samples. Of T/NK cells, CD8+ GNLY+ , CD8+ KLRC2+ T cells and FCGR3A+ NK cells were enriched in MPE but CD4+ FOXP3+ Tregs were enriched in PT samples. Naïve IGHD+ B and immune regulatory IGHA1+ B cells were largely identified in MPE, whereas bone metabolism-related CLEC11A+ B cells were significantly enriched in osteosarcoma PT. M2-type TAMs, including CLEC11A_TAM, C1QC_TAM and Prolif_TAMs, among myeloid cells were enriched in PT, which may suppress cytotoxicity activities of T cells through multiple ligand-receptor interactions. Mature LAMP3+ DCs were transformed from CD1C+ DC and CLEC9A+ DC sub-clusters when exposure to tumour alloantigens, which may improve T cell cytotoxicity activities on tumour cells under anti-PD-L1 treatments. In further, immune cells from MPE usually present up-regulated glycolysis and down-regulated oxidative phosphorylation and riboflavin metabolism activities compared to those in PT samples. CONCLUSIONS Our study provided a novel cellular atlas of MPE and PT in patients with advanced osteosarcoma, which may provide potential therapeutic targets in the future.
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Affiliation(s)
- Zhichang Zhang
- Orthopedic Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina,Clinical trial center of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai
China
| | - Weiping Ji
- Orthopedic Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Jin Huang
- Pathology Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Yawen Zhang
- Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Yan Zhou
- Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Jianjun Zhang
- Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Yang Dong
- Orthopedic Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Ting Yuan
- Orthopedic Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Qingcheng Yang
- Orthopedic Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Xiaomin Ding
- Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Lina Tang
- Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Hongtao Li
- Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Junyi Yin
- Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Yonggang Wang
- Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Tong Ji
- Department of Orthopaedics, Shanghai Ninth People's Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
| | - Jia Fei
- Department of Biochemistry and Molecular BiologyMedical College of Jinan UniversityGuangzhouChina
| | - Bing Zhang
- Orthopaedic Department of the Affiliated Hospital of Jiangxi University of Traditional Chinese MedicineNanchangChina
| | - Peizhan Chen
- Clinical Research Center, Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Haiyan Hu
- Clinical trial center of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai
China,Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
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Ribonucleic Acid Engineering of Dendritic Cells for Therapeutic Vaccination: Ready 'N Able to Improve Clinical Outcome? Cancers (Basel) 2020; 12:cancers12020299. [PMID: 32012714 PMCID: PMC7072269 DOI: 10.3390/cancers12020299] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 01/06/2020] [Accepted: 01/19/2020] [Indexed: 02/06/2023] Open
Abstract
Targeting and exploiting the immune system has become a valid alternative to conventional options for treating cancer and infectious disease. Dendritic cells (DCs) take a central place given their role as key orchestrators of immunity. Therapeutic vaccination with autologous DCs aims to stimulate the patient's own immune system to specifically target his/her disease and has proven to be an effective form of immunotherapy with very little toxicity. A great amount of research in this field has concentrated on engineering these DCs through ribonucleic acid (RNA) to improve vaccine efficacy and thereby the historically low response rates. We reviewed in depth the 52 clinical trials that have been published on RNA-engineered DC vaccination, spanning from 2001 to date and reporting on 696 different vaccinated patients. While ambiguity prevents reliable quantification of effects, these trials do provide evidence that RNA-modified DC vaccination can induce objective clinical responses and survival benefit in cancer patients through stimulation of anti-cancer immunity, without significant toxicity. Succinct background knowledge of RNA engineering strategies and concise conclusions from available clinical and recent preclinical evidence will help guide future research in the larger domain of DC immunotherapy.
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5
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Fatma F. Abdel Hamid, Mahmoud K. Singer, Mahmoud N. El-Rouby, Mahmoud M. Said, Reda H. Tabashy, Motawa E. El-Houseini. HepG2 Attenuation Induced by RNase A Modulates Gene Profiling and Immunophenotypic Characterization of Some Immune Cells Operating in Cancer Vaccine. JOURNAL OF CANCER RESEARCH UPDATES 2018; 7:27-34. [DOI: 10.6000/1929-2279.2018.07.01.3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/06/2025]
Abstract
Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer death. Attempts to induce an effective immune response against cancer by immunotherapeutic intervention, including activation of dendritic cells (DCs), were established. The present study was undertaken to investigate the attenuation of HepG2 cells using ribonuclease enzyme A (RNase A) as a possible biological factor to sensitize allogenic DCs and lymphocytes isolated from Egyptian HCC patients. Attenuation of HepG2 cells resulted in a significant increase in activated DC and T-lymphocyte markers, upregulation of CD44 gene expression and increased lactate dehydrogenase as well as interleukin-12 levels. In contrast, a significant decrease in mature DCs, B-cells, T-helper, cytotoxic T-cells, and NK-cells, as well as LMP-2 gene expression was recorded. In conclusion, the attenuation of HepG2 cells with RNase A and subsequent pulsation to allogenic DCs and lymphocytes caused a differential immune response. Further studies are recommended to explain the role of RNase A in modulating antigen expression on the tumor cell surface.
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6
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Hong YP, Li ZD, Prasoon P, Zhang Q. Immunotherapy for hepatocellular carcinoma: From basic research to clinical use. World J Hepatol 2015; 7:980-992. [PMID: 25954480 PMCID: PMC4419101 DOI: 10.4254/wjh.v7.i7.980] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 11/10/2014] [Accepted: 02/09/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a common cancer worldwide with a poor prognosis. Few strategies have been proven efficient in HCC treatment, particularly for those patients not indicated for curative resection or transplantation. Immunotherapy has been developed for decades for cancer control and is attaining more attention as a result of encouraging outcomes of new strategies such as chimeric antigen receptor T cells and immune checkpoint blockade. Right at the front of the new era of immunotherapy, we review the immunotherapy in HCC treatment, from basic research to clinical trials, covering anything from immunomodulators, tumor vaccines and adoptive immunotherapy. The mechanisms, efficacy and safety as well as the approach particulars are unveiled to assist readers to gain a concise but extensive understanding of immunotherapy of HCC.
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7
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Wirth TC. Spontaneous and therapeutic immune responses in hepatocellular carcinoma: implications for current and future immunotherapies. Expert Rev Gastroenterol Hepatol 2014; 8:101-10. [PMID: 24410473 DOI: 10.1586/17474124.2014.862497] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Hepatocellular carcinoma (HCC) represents a major health problem in the world, ranking fifth in incidence and third in cancer-related deaths. Due to the unique immunosuppressive microenvironment of the liver, HCC develops in an immunotolerant niche posing an important obstacle to immunotherapy. A number of studies, however, have shown immunogenic properties of HCC by demonstrating spontaneous adaptive immune responses during tumor formation and progression. Furthermore, studies examining immune responses during HCC therapy have revealed that conventional treatments such as surgical resection, locoregional therapy and systemic therapy with antibodies, small molecules or chemotherapy induce adaptive immune responses that contribute to therapeutic effects. These observations have provided a basis for clinical trials involving adoptive transfers of T cells or natural killer cells, peptide and dendritic cell vaccinations or, more recently, virotherapy and inhibition of co-inhibitory molecules. Here, spontaneous and therapeutic immune responses in HCC and their implication for current and future immunotherapies are discussed.
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Affiliation(s)
- Thomas C Wirth
- Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, 30625 Hannover, Germany
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8
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Benencia F. RNA vaccines for anti-tumor therapy. World J Exp Med 2013; 3:62-73. [DOI: 10.5493/wjem.v3.i4.62] [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: 07/30/2013] [Revised: 09/27/2013] [Accepted: 11/05/2013] [Indexed: 02/06/2023] Open
Abstract
The immune system is able to recognize tumor antigens and this has been the basis for the development of cancer immunotherapies. The immune system can be instructed to recognize and attack tumor cells by means of vaccination strategies. One such strategy involves the delivery of tumor antigen as genetic material. Herewith we describe the use of RNA encoding tumor antigens for vaccination purposes in tumor settings. RNA has features that are interesting for vaccination. Upon transfection, the RNA has no possibility of integration into the genome, and the tumor translated proteins enter the intrinsic antigen processing pathway thus enabling presentation by MHC-I molecules. This can specifically activate cytotoxic CD8 T cells that can attack and kill tumor cells. RNA can be delivered as a naked molecule for vaccination purposes or can be used to transfect dendritic cells. The combination of RNA technology with dendritic cell vaccination provides a powerful tool for cancer immunotherapies.
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9
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Clinical safety of induced CTL infusion through recombinant adeno-associated virus-transfected dendritic cell vaccination in Chinese cancer patients. Clin Transl Oncol 2012; 14:675-81. [DOI: 10.1007/s12094-012-0854-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Accepted: 12/06/2011] [Indexed: 11/26/2022]
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10
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Immunologic monitoring of cellular responses by dendritic/tumor cell fusion vaccines. J Biomed Biotechnol 2011; 2011:910836. [PMID: 21541197 PMCID: PMC3085507 DOI: 10.1155/2011/910836] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2010] [Revised: 11/11/2010] [Accepted: 02/27/2011] [Indexed: 12/22/2022] Open
Abstract
Although dendritic cell (DC)- based cancer vaccines induce effective antitumor activities in murine models, only limited therapeutic results have been obtained in clinical trials. As cancer vaccines induce antitumor activities by eliciting or modifying immune responses in patients with cancer, the Response Evaluation Criteria in Solid Tumors (RECIST) and WHO criteria, designed to detect early effects of cytotoxic chemotherapy in solid tumors, may not provide a complete assessment of cancer vaccines. The problem may, in part, be resolved by carrying out immunologic cellular monitoring, which is one prerequisite for rational development of cancer vaccines. In this review, we will discuss immunologic monitoring of cellular responses for the evaluation of cancer vaccines including fusions of DC and whole tumor cell.
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11
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Cathelin D, Nicolas A, Bouchot A, Fraszczak J, Labbé J, Bonnotte B. Dendritic cell-tumor cell hybrids and immunotherapy: what's next? Cytotherapy 2011; 13:774-85. [PMID: 21299362 DOI: 10.3109/14653249.2011.553593] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation still require optimization. An alternative technique for providing antigens to DC consists of the direct fusion of dendritic cells with tumor cells. These resulting hybrid cells may express both major histocompatibility complex (MHC) class I and II molecules associated with tumor antigens and the appropriate co-stimulatory molecules required for T-cell activation. Initially tested in animal models, this approach has now been evaluated in clinical trials, although with limited success. We summarize and discuss the results from the animal studies and first clinical trials. We also present a new approach to inducing hybrid formation by expression of viral fusogenic membrane glycoproteins.
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Affiliation(s)
- Dominique Cathelin
- Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 866, France.
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12
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Koido S, Hara E, Homma S, Ohkusa T, Gong J, Tajiri H. Cancer immunotherapy by fusions of dendritic cells and tumor cells. Immunotherapy 2011; 1:49-62. [PMID: 20635973 DOI: 10.2217/1750743x.1.1.49] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Dendritic cells (DCs) are potent professional antigen-presenting cells and play a critical role in the induction of primary immune responses. DC-based vaccination represents a potentially powerful strategy for cancer immunotherapy. Thus, the use of cancer vaccines to eliminate residual tumor cells is a promising area of investigation. The immunotherapy of tumor antigen-loaded DCs has now been demonstrated in cancer patients and some clinical responses without any significant toxicity. Fusions of DCs and tumor cells represent an alternative but promising approach to overcome the inability of tumor antigens to induce a sustainable T-cell response. This review deals with recent progress in the immunotherapy of cancer with fusions of DCs and tumor cells.
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Affiliation(s)
- Shigeo Koido
- Department of Internal Medicine, The Jikei University, Tokyo, Japan.
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Regulation of tumor immunity by tumor/dendritic cell fusions. Clin Dev Immunol 2010; 2010:516768. [PMID: 21048993 PMCID: PMC2964897 DOI: 10.1155/2010/516768] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2010] [Accepted: 09/22/2010] [Indexed: 02/07/2023]
Abstract
The goal of cancer vaccines is to induce antitumor immunity that ultimately will reduce tumor burden in tumor environment. Several strategies involving dendritic cells- (DCs)- based vaccine incorporating different tumor-associated antigens to induce antitumor immune responses against tumors have been tested in clinical trials worldwide. Although DCs-based vaccine such as fusions of whole tumor cells and DCs has been proven to be clinically safe and is efficient to enhance antitumor immune responses for inducing effective immune response and for breaking T-cell tolerance to tumor-associated antigens (TAAs), only a limited success has occurred in clinical trials. This paper reviews tumor immune escape and current strategies employed in the field of tumor/DC fusions vaccine aimed at enhancing activation of TAAs-specific cytotoxic T cells in tumor microenvironment.
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14
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Antigen-specific polyclonal cytotoxic T lymphocytes induced by fusions of dendritic cells and tumor cells. J Biomed Biotechnol 2010; 2010:752381. [PMID: 20379390 PMCID: PMC2850552 DOI: 10.1155/2010/752381] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2009] [Revised: 01/21/2010] [Accepted: 02/01/2010] [Indexed: 01/26/2023] Open
Abstract
The aim of cancer vaccines is induction of tumor-specific cytotoxic T lymphocytes (CTLs) that can reduce the tumor mass. Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Thus, DCs-based vaccination represents a potentially powerful strategy for induction of antigen-specific CTLs. Fusions of DCs and whole tumor cells represent an alternative approach to deliver, process, and subsequently present a broad spectrum of antigens, including those known and unidentified, in the context of costimulatory molecules. Once DCs/tumor fusions have been infused back into patient, they migrate to secondary lymphoid organs, where the generation of antigen-specific polyclonal CTL responses occurs. We will discuss perspectives for future development of DCs/tumor fusions for CTL induction.
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15
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Cancer vaccine by fusions of dendritic and cancer cells. Clin Dev Immunol 2010; 2009:657369. [PMID: 20182533 PMCID: PMC2825547 DOI: 10.1155/2009/657369] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2009] [Accepted: 12/09/2009] [Indexed: 12/23/2022]
Abstract
Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Therefore, their use for the active immunotherapy against cancers has been studied with considerable interest. The fusion of DCs with whole tumor cells represents in many ways an ideal approach to deliver, process, and subsequently present a broad array of tumor-associated antigens, including those yet to be unidentified, in the context of DCs-derived costimulatory molecules. DCs/tumor fusion vaccine stimulates potent antitumor immunity in the animal tumor models. In the human studies, T cells stimulated by DC/tumor fusion cells are effective in lysis of tumor cells that are used as the fusion partner. In the clinical trials, clinical and immunological responses were observed in patients with advanced stage of malignant tumors after being vaccinated with DC/tumor fusion cells, although the antitumor effect is not as vigorous as in the animal tumor models. This review summarizes recent advances in concepts and techniques that are providing new impulses to DCs/tumor fusions-based cancer vaccination.
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Ren J, Jia J, Zhang H, Zhang L, Ma B, Jiang H, Di L, Song G, Yu J. Dendritic cells pulsed with alpha-fetoprotein and mutant P53 fused gene induce bi-targeted cytotoxic T lymphocyte response against hepatic carcinoma. Cancer Sci 2008; 99:1420-6. [PMID: 18422751 PMCID: PMC11158406 DOI: 10.1111/j.1349-7006.2008.00820.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2007] [Revised: 03/04/2008] [Accepted: 03/11/2008] [Indexed: 11/27/2022] Open
Abstract
Dendritic cell (DC)-based immunotherapy is rapidly emerging as a promising treatment in cancer therapy. We had previously shown that DC pulsed with either defined mRNA of tumor antigen (Ag) such as alpha-fetoprotein (AFP), or total RNA of hepatocellular carcinoma (HCC) could elicit Ag-specific cytotoxic T lymphocyte (CTL) response. Therefore, we suggested a novel DC-based therapeutic method, in which DCs derived from CD34(+) cells enriched peripheral blood mononuclear cells were pulsed with liposome-coated AFP and mutant P53 (mtP53) fused gene pEGFP-C3/AFP-mtP53 to induce bi-targeted specific CTL responses against HCC. Three different genotype HCC cell lines, HepG2 (human histocompatibility leukocyte antigens (HLA) A2 positive, AFP expressing positive, P53 expressing negative), SMMC7721 (HLA A2 positive, neither AFP nor P53 expressing positive), and HMCC97 (HLA A2 positive, both AFP and P53 expressing positive) were selected as targets for CTL responses. An important finding was that DCs pulsed with the liposome-coated fused gene could evoke more intensive bi-targeted Ag-specific CTL responses against HMCC97 than DCs pulsed with either AFP or P53 single gene (P < 0.05). This experimental therapeutic model provides a new promising cytotherapeutic approach, in that DCs pulsed with the fused gene of different Ags might induce more extensive multitargeted antitumor immunity.
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Affiliation(s)
- Jun Ren
- Department of Medical Oncology, Peking University School of Oncology/Beijing Cancer Hospital, No. 52 Fucheng Rd, Beijing, China 100036.
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Prieto J, Fernandez-Ruiz V, Kawa MP, Sarobe P, Qian C. Cells as vehicles for therapeutic genes to treat liver diseases. Gene Ther 2008; 15:765-71. [DOI: 10.1038/gt.2008.44] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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