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Review
. 2023 Jan-Feb;29(1):28-33.
doi: 10.1097/PPO.0000000000000636.

Chimeric Antigen Receptor T-Cell Therapy: Current Perspective on T Cell-Intrinsic, T Cell-Extrinsic, and Therapeutic Limitations

Shawna K Brookens  1 , Avery D Posey Jr
Affiliations
Review

Chimeric Antigen Receptor T-Cell Therapy: Current Perspective on T Cell-Intrinsic, T Cell-Extrinsic, and Therapeutic Limitations

Shawna K Brookens et al. Cancer J. 2023 Jan-Feb.

Abstract

Genetically engineered chimeric antigen receptor (CAR) T-cell therapy leverages the ability of the immune system to eliminate tumors and redirects cytotoxic functions toward cells expressing specified tumor-restricted antigens. Although 6 CAR T-cell therapies have received Food and Drug Administration (FDA) approval for the treatment of many hematological malignancies, limitations involving T cell-intrinsic, T cell-extrinsic, and therapeutic factors remain in the treatment of both liquid and solid tumors. Chimeric antigen receptor design, signals from the tumor microenvironment, tumor antigen escape mechanisms, and systemic inflammatory consequences of CAR T-cell infusion all influence the efficacy and feasibility of CAR T-cell therapy in different malignancies. Here, we review the core structure of the CAR, the evolution of different CAR generations, CAR T-cell therapy limitations, and current strategies being investigated to overcome the T cell-intrinsic, T cell-independent, and therapeutic barriers to successful CAR T-cell therapy.

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Conflict of interest statement

Conflicts of Interest and Sources of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. A.D.P. is supported by funding from the Department of Veterans Affairs (IK2BX004183), Lustgarten Foundation-AACR, V Foundation, and the National Foundation for Cancer Research. S.K.B. is supported by the UNCF Bristol-Myers Squibb E.E. Just Postgraduate Fellowship in the Life Sciences.

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