Car-T Cell Therapy: A Paradigm Shift in Cancer Treatment

Authors

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy, a major application of precision and customized medicine, has emerged as a revolutionary advancement in cancer immunotherapy. CAR-T therapy genetically alters a patient's T cells to express synthetic receptors that accurately identify tumor-associated antigens in an MHC-independent manner, resulting in potent and targeted anticancer activity. This study provides an overview of the fundamental ideas of CAR-T cell therapy, including T-cell biology, CAR structure and generations, and the production process, which includes leukapheresis, genetic engineering, ex vivo expansion, conditioning chemotherapy, and patient injection. The mechanisms underlying CAR-T-mediated tumor destruction include antigen recognition, T-cell activation, cytotoxic effector pathways, cytokine production, and tumor lysis. We examine the most recent FDA-approved CAR-T treatments and their clinical applications. We also discuss novel applications in solid tumors and associated issues, such as immune-suppressive tumor microenvironment and antigen heterogeneity. The primary adverse effects, such as immune effector cell-associated neurotoxicity syndrome and cytokine release syndrome, are also discussed in the review along with current treatments. Finally, the drawbacks of CAR-T therapy, recent advances in technology, and the evolving CAR-T environment in India including domestic innovations are examined.

Keywords: Tumor; Cancer immunotherapy; Precision medicine; Cytokine release syndrom

Keywords:

Tumor, Cancer immunotherapy, Precision medicine, Cytokine release syndrome

DOI

https://doi.org/10.22270/jddt.v16i3.7599

Author Biographies

Pratiksha Hajare , PES’s Modern College of Pharmacy Nigdi, Pune 411044

PES’s Modern College of Pharmacy Nigdi, Pune 411044

Rachana Satish Lokhande , PES’s Modern College of Pharmacy Nigdi, Pune 411044

PES’s Modern College of Pharmacy Nigdi, Pune 411044

Nikita Sarjerao Game , PES’s Modern College of Pharmacy Nigdi, Pune 411044

PES’s Modern College of Pharmacy Nigdi, Pune 411044

Shatakshi Prakash Patki , PES’s Modern College of Pharmacy Nigdi, Pune 411044

PES’s Modern College of Pharmacy Nigdi, Pune 411044

References

1. Tan S, Li D, Zhu X. Cancer immunotherapy: Pros, cons and beyond. Biomedicine & Pharmacotherapy. 2020 Apr 1;124:109821.https://doi.org/10.1016/j.biopha.2020.109821

2. Almåsbak H, Aarvak T, Vemuri MC. CAR T cell therapy: a game changer in cancer treatment. Journal of immunology research. 2016;2016(1):5474602. https://doi.org/10.1155/2016/5474602

3. Patel KK, Tariveranmoshabad M, Kadu S, Shobaki N, June C. From concept to cure: The evolution of CAR-T cell therapy. Molecular Therapy. 2025 May 7;33(5):2123-40. https://doi.org/10.1016/j.ymthe.2025.03.005

4. Awasthi R, Maier HJ, Zhang J, Lim S. Kymriah®(tisagenlecleucel)–an overview of the clinical development journey of the first approved CAR-T therapy. Human vaccines & immunotherapeutics. 2023 Jan 2;19(1):2210046.https://doi.org/10.1080/21645515.2023.2210046

5. Zhu C, Wang F, Cheng Z, Zhang L, Li H. Precise CAR-T-cell Therapy Targeting Non-Cancerous Diseases: Advances in Precision Medicine and Bioengineering. Precision Medicine and Engineering. 2025 Mar 10:100024.https://doi.org/10.1016/j.preme.2025.100024

6. Ahmad U, Khan Z, Ualiyeva D, Amissah OB, Noor Z, Khan A, Zaman N, Khan M, Khan A, Ali B. Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities; A comprehensive review. Advances in Cancer Biology-Metastasis. 2022 Jul 1;4:100035.https://doi.org/10.1016/j.adcanc.2022.100035

7. Chmielewski M, Abken H. TRUCKs: the fourth generation of CARs. Expert opinion on biological therapy. 2015 Aug 3;15(8):1145-54. https://doi.org/10.1517/14712598.2015.1046430

8. Sadelain M, Brentjens R, Rivière I. The basic principles of chimeric antigen receptor design. Cancer discovery. 2013 Apr 1;3(4):388-98.https://doi.org/10.1158/2159-8290.CD-12-0548

9. Pessach I, Nagler A. Leukapheresis for CAR-T cell production and therapy. Transfusion and Apheresis Science. 2023 Dec 1;62(6):103828.https://doi.org/10.1016/j.transci.2023.103828

10. Mehrabadi AZ, Ranjbar R, Farzanehpour M, Shahriary A, Dorostkar R, Hamidinejad MA, Ghaleh HE. Therapeutic potential of CAR T cell in malignancies: A scoping review. Biomedicine & Pharmacotherapy. 2022 Feb 1;146:112512.https://doi.org/10.1016/j.biopha.2021.112512

11. Strati P, Jallouk AP, Sun R, Choi J, Das K, Cherng HJ, Ahmed S, Lee HJ, Iyer SP, Nair R, Nastoupil LJ. Impact of conditioning chemotherapy on lymphocyte kinetics and outcomes in LBCL patients treated with CAR T-cell therapy. Leukemia. (2022) Nov;36(11):2669-77. https://doi.org/10.1038/s41375-022-01704-z

12. Dannenfelser R, Allen GM, VanderSluis B, Koegel AK, Levinson S, Stark SR, Yao V, Tadych A, Troyanskaya OG, Lim WA. Discriminatory power of combinatorial antigen recognition in cancer T cell therapies. Cell systems. (2020) Sep 23;11(3):215-28. https://doi.org/10.1016/j.cels.2020.08.002

13. Lim WA, June CH. The principles of engineering immune cells to treat cancer. cell. 2017 Feb 9;168(4):724-40.https://doi.org/10.1016/j.cell.2017.01.016

14. Benmebarek MR, Karches CH, Cadilha BL, Lesch S, Endres S, Kobold S. Killing mechanisms of chimeric antigen receptor (CAR) T cells. International journal of molecular sciences. (2019) Mar 14;20(6):1283. https://doi.org/10.3390/ijms20061283

15. Silveira CR, Corveloni AC, Caruso SR, Macêdo NA, Brussolo NM, Haddad F, Fernandes TR, de Andrade PV, Orellana MD, Guerino-Cunha RL. Cytokines as an important player in the context of CAR-T cell therapy for cancer: their role in tumor immunomodulation, manufacture, and clinical implications. Frontiers in Immunology. (2022) Sep 12;13:947648. https://doi.org/10.3389/fimmu.2022.947648

16. Zhang Q, Zu C, Jing R, Feng Y, Zhang Y, Zhang M, Lv Y, Cui J, Zhou L, Meng Y, Wang L. Incidence, clinical characteristics and prognosis of tumor lysis syndrome following B-cell maturation antigen-targeted chimeric antigen receptor-T cell therapy in relapsed/refractory multiple myeloma. Frontiers in Immunology. (2023) May 4;14:1125357. https://doi.org/10.3389/fimmu.2023.1125357

17. Miao L, Zhang Z, Ren Z, Li Y. Reactions related to CAR-T cell therapy. Frontiers in immunology. 2021 Apr 28;12:663201.https://doi.org/10.3389/fimmu.2021.663201

18. Asmamaw Dejenie T, Tiruneh G/Medhin M, Dessie Terefe G, Tadele Admasu F, Wale Tesega W, Chekol Abebe E. Current updates on generations, approvals, and clinical trials of CAR T-cell therapy. Human vaccines & immunotherapeutics. (2022) Nov 30;18(6):2114254. https://doi.org/10.1080/21645515.2022.2114254

19. Escobar G, Berger TR, Maus MV. CAR-T cells in solid tumors: Challenges and breakthroughs. Cell Reports Medicine. 2025 Nov 18;6(11). https://doi.org/10.1016/j.xcrm.2025.102353

20. Fonkoua LA, Sirpilla O, Sakemura R, Siegler EL, Kenderian SS. CAR T cell therapy and the tumor microenvironment: Current challenges and opportunities. Molecular Therapy-Oncolytics. 2022 Jun 16;25:69-77.https://doi.org/10.1016/j.omto.2022.03.009

21. Qin Y, Xu G. Enhancing CAR T-cell therapies against solid tumors: Mechanisms and reversion of resistance. Frontiers in Immunology. 2022 Dec 8;13:1053120.https://doi.org/10.3389/fimmu.2022.1053120

22. Gargett T, Brown MP. The inducible caspase-9 suicide gene system as a “safety switch” to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells. Frontiers in pharmacology. 2014 Oct 28;5:235.https://doi.org/10.3389/fphar.2014.00235

23. Levine BL, Miskin J, Wonnacott K, Keir C. Global manufacturing of CAR T cell therapy. Molecular therapy Methods & clinical development. 2017 Mar 17;4:92-101. https://doi.org/10.1016/j.omtm.2016.12.006

24. Shah M, Krull A, Odonnell L, de Lima MJ, Bezerra E. Promises and challenges of a decentralized CAR T-cell manufacturing model. Frontiers in Transplantation. 2023 Sep 5;2:1238535. https://doi.org/10.3389/frtra.2023.1238535

25. Le RQ, Li L, Yuan W, Shord SS, Nie L, Habtemariam BA, Przepiorka D, Farrell AT, Pazdur R. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell‐induced severe or life‐threatening cytokine release syndrome. The oncologist. (2018) Aug 1;23(8):943-7. https://doi.org/10.1634/theoncologist.2018-0028

26. Sterner RC, Sterner RM. Immune effector cell associated neurotoxicity syndrome in chimeric antigen receptor-T cell therapy. Frontiers in immunology. (2022) Aug 23;13:879608. https://doi.org/10.3389/fimmu.2022.879608

27. Gu T, Hu K, Si X, Hu Y, Huang H. Mechanisms of immune effector cell‐associated neurotoxicity syndrome after CAR‐T treatment. WIREs mechanisms of disease. (2022)Nov;14(6):1576. https://doi.org/10.1002/wsbm.1576

28. Zhang Y, Li Y, Cao W, Wang F, Xie X, Li Y, Wang X, Guo R, Jiang Z, Guo R. Single-cell analysis of target antigens of CAR-T reveals a potential landscape of “on-target, off-tumor toxicity”. Frontiers in immunology. (2021) Dec 16;12:799206. https://doi.org/10.3389/fimmu.2021.799206

29. Kampouri E, Little JS, Rejeski K, Manuel O, Hammond SP, Hill JA. Infections after chimeric antigen receptor (CAR)‐T‐cell therapy for hematologic malignancies. Transplant Infectious Disease. 2023 Nov;25:e14157. https://doi.org/10.1111/tid.14157

30. Gómez-Melero S, Hassouneh F, Vallejo-Bermúdez IM, Agüera-Morales E, Solana R, Caballero-Villarraso J. Tandem CAR-T cell therapy: recent advances and current challenges. Frontiers in Immunology. 2025 Feb 28;16:1546172. https://doi.org/10.3389/fimmu.2025.1546172

31. Lu H, Zhao X, Li Z, Hu Y, Wang H. From CAR-T cells to CAR-NK cells: a developing immunotherapy method for hematological malignancies. Frontiers in Oncology. (2021) Aug 6;11:720501. https://doi.org/10.3389/fonc.2021.720501

32. Chen S, van den Brink MR. Allogeneic “Off-the-Shelf” CAR T cells: Challenges and advances. Best Practice & Research Clinical Haematology. (2024) Sep 1;37(3):101566. https://doi.org/10.1016/j.beha.2024.101566

33. Nguyen TT, Thanh Nhu N, Chen CL, Lin CF. Effectiveness and safety of CD22 and CD19 dual‐targeting chimeric antigen receptor T‐cell therapy in patients with relapsed or refractory B‐cell malignancies: A meta‐analysis. Cancer Medicine.(2023)Sep;12(18):18767-85. https://doi.org/10.1002/cam4.6497

34. Eissenberg LG, Rettig M, Dehdashti F, Piwnica-Worms D, DiPersio JF. Suicide genes: monitoring cells in patients with a safety switch. Frontiers in Pharmacology. 2014 Nov 6;5:241. https://doi.org/10.3389/fphar.2014.00241

35. Bedford P, Jy J, Collins L, Keizer S. Considering cell therapy product “good manufacturing practice” status. Frontiers in medicine. (2018) Apr 30;5:118. https://doi.org/10.3389/fmed.2018.00118

36. Sengsayadeth S, Savani BN, Oluwole O, Dholaria B. Overview of approved CAR‐T therapies, ongoing clinical trials, and its impact on clinical practice. EJHaem. 2022 Jan;3:6-10 https://doi.org/10.1002/jha2.338

37. Huang R, Li X, He Y, Zhu W, Gao L, Liu Y, Gao L, Wen Q, Zhong JF, Zhang C, Zhang X. Recent advances in CAR-T cell engineering. Journal of hematology & oncology. 2020 Jul 2;13(1):86. https://doi.org/10.1186/s13045-020-00910-5

38. Ramsay AG. Immune checkpoint blockade immunotherapy to activate anti‐tumour T‐cell immunity. British journal of haematology. 2013 Aug;162(3):313-25.https://doi.org/10.1111/bjh.12380

39. Santomasso B, Bachier C, Westin J, Rezvani K, Shpall EJ. The other side of CAR T-cell therapy: cytokine release syndrome, neurologic toxicity, and financial burden. InAmerican society of clinical oncology educational book. American Society of Clinical Oncology. Annual Meeting 2019 Jan 1 (Vol. 39, pp. 433-444).https://doi.org/10.1200/edbk_238691

40. Gu X, Zhang Y, Zhou W, Wang F, Yan F, Gao H, Wang W. Infusion and delivery strategies to maximize the efficacy of CAR-T cell immunotherapy for cancers. Experimental Hematology & Oncology. 2024 Jul 26;13(1):70. https://doi.org/10.1186/s40164-024-00542-2

41. Frey NV. Approval of brexucabtagene autoleucel for adults with relapsed and refractory acute lymphocytic leukemia. Blood, The Journal of the American Society of Hematology. 2022 Jul 7;140(1):11-5. https://doi.org/10.1182/blood.2021014892

42. Neelapu SS. Managing the toxicities of CAR T‐cell therapy. Hematological oncology. 2019 Jun;37:48-52. https://doi.org/10.1002/hon.2595

43. Ravindranath A, Dubey A, Suresh S, Chaudhuri G, Chirmule N. CAR-T cell therapy in India requires a paradigm shift in training, education and health care processes. Cytotherapy. 2022 Feb 1;24(2):101-9 https://doi.org/10.1016/j.jcyt.2021.09.007

44. Eyles JE, Vessillier S, Jones A, Stacey G, Schneider CK, Price J. Cell therapy products: focus on issues with manufacturing and quality control of chimeric antigen receptor T‐cell therapies. Journal of Chemical Technology & Biotechnology. 2019 Apr;94(4):1008-16.https://doi.org/10.1002/jctb.5829

45. Zhao J, Song Y, Liu D. Clinical trials of dual-target CAR T cells, donor-derived CAR T cells, and universal CAR T cells for acute lymphoid leukemia. Journal of hematology & oncology. 2019 Feb 14;12(1):17. https://doi.org/10.1186/s13045-019-0705-x

46. Kopmar NE, Cassaday RD. Clinical insights on brexucabtagene autoleucel for the treatment of patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Cancer Management and Research. 2024 Dec 31:1587-96. https://doi.org/10.2147/CMAR.S379807

47. Rodriguez-Garcia A, Palazon A, Noguera-Ortega E, Powell Jr DJ, Guedan S. CAR-T cells hit the tumor microenvironment: strategies to overcome tumor escape. Frontiers in immunology. 2020 Jun 17;11:1109. https://doi.org/10.3389/fimmu.2020.01109

48. Penack O, Koenecke C. Complications after CD19+ CAR T-cell therapy. Cancers. 2020 Nov 19;12(11):3445. https://doi.org/10.3390/cancers12113445

49. Hay AE, Cheung MC. CAR T-cells: costs, comparisons, and commentary. Journal of Medical Economics. 2019 Jul 3;22(7):613-5.https://doi.org/10.1080/13696998.2019.1582059

50. Martinez M, Moon EK. CAR T cells for solid tumors: new strategies for finding, infiltrating, and surviving in the tumor microenvironment. Frontiers in immunology. 2019 Feb 5;10:128.https://doi.org/10.3389/fimmu.2019.00128

Published

2026-03-15
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How to Cite

1.
Hajare P, Lokhande RS, Game NS, Patki SP. Car-T Cell Therapy: A Paradigm Shift in Cancer Treatment. J. Drug Delivery Ther. [Internet]. 2026 Mar. 15 [cited 2026 Apr. 18];16(3):192-9. Available from: https://www.jddtonline.info/index.php/jddt/article/view/7599

How to Cite

1.
Hajare P, Lokhande RS, Game NS, Patki SP. Car-T Cell Therapy: A Paradigm Shift in Cancer Treatment. J. Drug Delivery Ther. [Internet]. 2026 Mar. 15 [cited 2026 Apr. 18];16(3):192-9. Available from: https://www.jddtonline.info/index.php/jddt/article/view/7599