CAR-T THERAPY: MECHANISMS OF ACTION, CLINICAL APPLICATIONS AND FUTURE DIRECTIONS
DOI:
https://doi.org/10.31435/ijitss.2(50).2026.5693Keywords:
CAR-T Cells, Immunotherapy, Hematologic Malignancies, Solid Tumors, Cytokine Release Syndrome, Cancer TherapyAbstract
Chimeric antigen receptor T-cell (CAR-T) therapy represents a major advancement in cancer immunotherapy, introducing a novel therapeutic approach based on the genetic modification of T lymphocytes to enhance tumor-specific cytotoxicity. This strategy has significantly transformed the treatment landscape, particularly in hematologic malignancies. The aim of this review is to summarize the current state of knowledge regarding CAR-T therapy, including its mechanisms of action, clinical applications, toxicity profile, limitations, and future directions of development. A narrative review of the literature was conducted based on selected publications indexed in biomedical databases, with particular emphasis on recent advances in both hematologic and solid tumors. CAR-T therapy has demonstrated high clinical efficacy in hematologic malignancies, especially B-cell cancers such as acute lymphoblastic leukemia and multiple myeloma, achieving substantial response rates in patients with relapsed or refractory disease. In contrast, its application in solid tumors remains limited due to challenges including antigen heterogeneity, an immunosuppressive tumor microenvironment, and reduced T-cell infiltration. The therapy is associated with characteristic toxicities, most notably cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, which require careful monitoring and management. Furthermore, its broader implementation is constrained by complex manufacturing processes, high costs, and limited accessibility. Ongoing research focuses on improving CAR-T cell persistence, overcoming T-cell exhaustion, optimizing antigen targeting, and developing novel strategies such as allogeneic products and combination therapies. In conclusion, CAR-T therapy constitutes a transformative modality in modern oncology, with established efficacy in hematologic malignancies and emerging potential in solid tumors, and its continued development is expected to further expand its clinical utility.
References
Zhang, M., & Liu, C. (2025). Advances in cancer immunotherapy: Historical perspectives, current developments, and future directions. Molecular Cancer, 24(1), 136.
Prazeres, P. H. D. M., & da Silva, G. H. C. (2025). Advancing cancer immunotherapy using lipid nanoparticle-based approaches. International Journal of Nanomedicine, 20, 12283–12305.
Wang, M., & Yu, F. (2025). Present and future of cancer nano-immunotherapy: Opportunities, obstacles and challenges. Molecular Cancer, 24(1), 26.
Huang, Y., & Cao, R. (2025). In vivo CAR-T cell therapy: New breakthroughs for cell-based tumor immunotherapy. Human Vaccines & Immunotherapeutics, 21(1), 2558403.
Kuttiappan, A., & Chenchula, S. (2025). CAR T-cell therapy in hematologic and solid malignancies: Mechanisms, clinical applications, and future directions. Medical Oncology, 42(9), 376.
Chen, A. X. Y., & Yap, K. M. (2025). Rewiring endogenous genes in CAR T cells for tumour-restricted payload delivery. Nature, 644(8075), 241–251.
Yaacoub, S., & Vannoy, E. (2025). CAR-T cell therapy in brain malignancies: Obstacles in the face of cellular trafficking and persistence. Frontiers in Immunology, 16, 1596499.
Eksteen, C., & Riedemann, J. (2025). CAR T-cell therapy as a promising immunotherapeutic approach for medulloblastoma. Revue Neurologique (Paris), 181(8), 703–712.
Ali, A., & Ozdemirli, M. (2026). Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders. Nature Reviews Clinical Oncology. Advance online publication.
Rampotas, A., & Roddie, C. (2025). The present and future of CAR T-cell therapy for adult B-cell ALL. Blood, 145(14), 1485–1497.
Dima, D., & Banerjee, R. (2025). CAR T-cell therapy and bispecific antibodies in the management of multiple myeloma. Hematology, American Society of Hematology Education Program, 2025(1), 324–333.
Velasco, R., & Abad-Inchaurrondo, I. (2025). CAR-T cell-associated neurotoxicity during therapy of hematologic malignancies: Incidence, clinical features, predictive biomarkers and management measures. Leukemia & Lymphoma, 66(9), 1557–1569.
Richardson, T., & Holtick, U. (2025). Sequential BCMA CAR T-cell therapy in refractory multiple myeloma. Blood Advances, 9(18), 4624–4630.
Li, J., & Liu, C. (2025). Optimizing CAR T cell therapy for solid tumours: A clinical perspective. Nature Reviews Clinical Oncology, 22(12), 953–968.
Uslu, U., & June, C. H. (2025). Beyond the blood: Expanding CAR T cell therapy to solid tumors. Nature Biotechnology, 43(4), 506–515.
Khan, S. H., & Choi, Y. (2025). Advances in CAR T cell therapy: Antigen selection, modifications, and current trials for solid tumors. Frontiers in Immunology, 15, 1489827.
Zhao, Z., & Li, Q. (2025). A collagenase nanogel backpack improves CAR-T cell therapy outcomes in pancreatic cancer. Nature Nanotechnology, 20(8), 1131–1141.
Sadowski, K., & Ploch, W. (2025). Nephrotoxicity in CAR-T cell therapy. Transplantation and Cellular Therapy, 31(7), 407–418.
Velasco, R., & Abad-Inchaurrondo, I. (2025). CAR-T cell-associated neurotoxicity during therapy of hematologic malignancies: Incidence, clinical features, predictive biomarkers and management measures. Leukemia & Lymphoma, 66(9), 1557–1569.
Morris, E. C., & Neelapu, S. S. (2022). Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nature Reviews Immunology, 22(2), 85–96.
Brudno, J. N., & Kochenderfer, J. N. (2024). Current understanding and management of CAR T cell-associated toxicities. Nature Reviews Clinical Oncology, 21(7), 501–521.
Xiao, X., & Huang, S. (2021). Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies. Journal of Experimental & Clinical Cancer Research, 40(1), 367.
Boulch, M., & Cazaux, M. (2023). A major role for CD4+ T cells in driving cytokine release syndrome during CAR T cell therapy. Cell Reports Medicine, 4(9), 101161.
Chohan, K. L., & Siegler, E. L. (2023). CAR-T cell therapy: The efficacy and toxicity balance. Current Hematologic Malignancy Reports, 18(2), 9–18.
Ai, K., & Liu, B. (2024). Optimizing CAR-T cell therapy for solid tumors: Current challenges and potential strategies. Journal of Hematology & Oncology, 17(1), 105.
Abdo, L., & Batista-Silva, L. R. (2025). Cost-effective strategies for CAR-T cell therapy manufacturing. Molecular Therapy—Oncolytics, 33(2), 200980.
Dagar, G., & Gupta, A. (2023). Harnessing the potential of CAR-T cell therapy: Progress, challenges, and future directions in hematological and solid tumor treatments. Journal of Translational Medicine, 21(1), 449.
Ong, M. Z., & Kimberly, S. A. (2024). FDA-approved CAR T-cell therapy: A decade of progress and challenges. Current Pharmaceutical Biotechnology, 25(11), 1377–1393.
Odstrcil, M. S., & Lee, C. J. (2024). Access to CAR T-cell therapy: Focus on diversity, equity and inclusion. Blood Reviews, 63, 101136.
Lei, J., & Ni, Z. (2025). Universal CAR-T cell therapy for cancer treatment: Advances and challenges. Oncology Research, 33(11), 3347–3373.
Khan, A. N., & Asija, S. (2024). CAR-T cell therapy in hematological malignancies: Where are we now and where are we heading for? European Journal of Haematology, 112(1), 6–18.
Zhang, X., & Zhang, H. (2023). CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies. Frontiers in Immunology, 14, 1101495.
Gumber, D., & Wang, L. D. (2022). Improving CAR-T immunotherapy: Overcoming the challenges of T cell exhaustion. EBioMedicine, 77, 103941.
Ai, K., & Liu, B. (2024). Optimizing CAR-T cell therapy for solid tumors: Current challenges and potential strategies. Journal of Hematology & Oncology, 17(1), 105.
Jogalekar, M. P., & Rajendran, R. L. (2022). CAR T-cell-based gene therapy for cancers: New perspectives, challenges, and clinical developments. Frontiers in Immunology, 13, 925985.
Pfeffer, L. K., & Fischbach, F. (2025). Current state and perspectives of CAR T cell therapy in central nervous system diseases. Brain, 148(3), 723–736.
Farhangnia, P., & Khorramdelazad, H. (2024). Current and future immunotherapeutic approaches in pancreatic cancer treatment. Journal of Hematology & Oncology, 17(1), 40.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Mateusz Winkler, Julia Bezak, Aleksandra Arczewska, Michał Zaborowski, Klaudia Purgał-Zaborowska, Klaudia Michałowska, Oliwier Kolanowski, Olga Turzańska, Szymon Marciszuk

This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.

