Arjumand S, Raj A, Prattay KMR, Omer HBM, Azam F. Chimeric antigen receptor T cell therapy: Revolutionizing cancer treatment. World J Clin Oncol 2025; 16(11): 108667 [PMID: 41355907 DOI: 10.5306/wjco.v16.i11.108667]
Corresponding Author of This Article
Faruque Azam, Lecturer, Research Fellow, School of Pharmacy, BRAC University, Kha 224, Pragati Sarani, Merul Badda, Dhaka 1212, Bangladesh. faruque.azam@bracu.ac.bd
Research Domain of This Article
Oncology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Nov 24, 2025; 16(11): 108667 Published online Nov 24, 2025. doi: 10.5306/wjco.v16.i11.108667
Chimeric antigen receptor T cell therapy: Revolutionizing cancer treatment
Samarah Arjumand, Asef Raj, Kazi Milenur Rahman Prattay, Humair Bin Md Omer, Faruque Azam
Samarah Arjumand, Asef Raj, Kazi Milenur Rahman Prattay, Humair Bin Md Omer, Faruque Azam, School of Pharmacy, BRAC University, Dhaka 1212, Bangladesh
Faruque Azam, Evidence Based Medicine Research Group, School of Pharmacy, BRAC University, Dhaka 1212, Bangladesh
Co-first authors: Samarah Arjumand and Asef Raj.
Author contributions: Arjumand S and Raj A contributed equally to this work; Arjumand S, Raj A and Azam F conceptualized and designed the manuscript; Arjumand S, Raj A and Prattay KMR conducted the literature review and data collection; Arjumand S and Prattay KMR prepared the artwork and illustrations; Arjumand S, Raj A, and Prattay KMR drafted the manuscript; Omer HBM and Azam F critically reviewed and edited the content; all authors read and approved the final version of the manuscript.
Conflict-of-interest statement: The authors declare no conflicts of interest related to this work.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Faruque Azam, Lecturer, Research Fellow, School of Pharmacy, BRAC University, Kha 224, Pragati Sarani, Merul Badda, Dhaka 1212, Bangladesh. faruque.azam@bracu.ac.bd
Received: April 20, 2025 Revised: June 22, 2025 Accepted: October 10, 2025 Published online: November 24, 2025 Processing time: 215 Days and 17.8 Hours
Abstract
Chimeric antigen receptor T (CAR-T) cell therapy represents a major advance in cancer immunotherapy, offering targeted treatment options, particularly for hematologic malignancies. This review comprehensively explores the structural evolution, production processes, and cytotoxic mechanisms underlying CAR-T function. Therapy involves engineering autologous T cells with synthetic receptors that allow major histocompatibility complex-independent recognition of tumor-associated antigens. Key structural components such as antigen recognition domains, spacers, transmembrane, and intracellular domains are optimized to enhance specificity, persistence, and cytotoxicity. CAR-T therapy exerts antitumor effects via granzyme-perforin degranulation, Fas/Fas ligand signaling, and cytokine secretion. Over time, the development of second- to fifth-generation CARs has incorporated costimulatory molecules, transcriptional regulation, and logic-gated control to improve efficacy and safety. Additionally, novel engineering strategies such as dual CARs, tandem CARs, SynNotch systems, and universal or inhibitory CARs have expanded antigen targeting and reduced off-tumor toxicity. Emerging gene delivery technologies, including viral vectors, transposons, CRISPR/Cas9, and RNA-based electroporation, are improving CAR-T production. Despite notable clinical success, particularly in CD19- and B-cell maturation antigen-targeted therapies, CAR-T applications face challenges, including cell exhaustion, antigen escape, and therapy-induced toxicities, such as cytokine release syndrome and neurotoxicity. Ongoing efforts in engineering innovation, clinical trials, and regulatory support continue to shape CAR-T therapy into a safer, more precise tool for cancer treatment. This review highlights current advances while outlining the barriers and future prospects of CAR-T immunotherapy.
Core Tip: This review presents a comprehensive and forward-looking analysis of chimeric antigen receptor T cell (CAR-T) therapy, detailing its structural evolution, manufacturing strategies, and cytotoxic mechanisms. It uniquely integrates emerging advances, such as dual chimeric antigen receptors, SynNotch systems, and universal CAR-T designs. The manuscript also addresses clinical challenges, like antigen escape and cytokine release syndrome, and highlights innovative gene delivery technologies, including viral vectors, CRISPR/Cas9, and RNA-based methods. This work offers a consolidated and insightful resource for researchers and clinicians aiming to advance CAR-T therapy toward safer and more effective cancer treatments.
