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

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.

Automated summary

Genetically engineered CAR T-cell therapy makes use of the immune system to eliminate tumors and redirect cytotoxic functions towards cells expressing specific tumor-restricted antigens. Despite FDA approval for 6 CAR T-cell therapies in hematological malignancies, there are limitations in the treatment of both liquid and solid tumors involving T cell-intrinsic, T cell-extrinsic, and therapeutic factors. This review discusses the core structure of CAR, the evolution of different CAR generations, limitations of CAR T-cell therapy, and current strategies to overcome barriers for successful therapy.