CAR-T-Cell Therapy: Present Progress and Future strategies

Abstract

Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy that uses the patient's immune system. It creates cancer-killing T cells through genetic modification that targets tumor antigens. CAR consists of three fundamental units, the extracellular, transmembrane, and intracellular domains. CARs are rapidly evolving with progress in the field of immunotherapy starting from first-generation CARs to next-generation CARs. Different cancer types, including B-cell malignancies, are being treated by CAR-T therapy. The FDA has approved two CAR-T therapies, namely, tisagenlecleucel and axicabtagene ciloleucel. The recently approved CAR-T products are Lisocabtagene maraleucel and Idecabtagene vicleucel. Despite the success of CAR-T therapy, several limitations, including cytokine release syndrome and neurotoxicity, need to be overcome. In the present review, we have provided an overview of CAR generations, their applications, potential limitations, and possible solutions for improving CAR-T therapy for a variety of tumor types.

Current updates on generations, approvals, and clinical trials of CAR T-cell therapy

“…The activated CAR T-cells then undergo extensive proliferation and differentiation, which is essential for the effector functions or cancer-killing activities of the CAR T-cells. 123 , 127 …”

Steering the course of CAR T cell therapy with lipid nanoparticles

“…Given this success, the U.S. Food and Drug Administration (FDA) approves six CAR products, as outlined in Table 1 . Earlier, we showcased nanoengineering of better performing CAR T cells [ 17 ], mitigating the barriers of the tumor microenvironment (TME) [ 18 ] and precision in targeting hematological and solid cancers [ 19 ] (Fig. 1 A).…”

From barriers to novel strategies: smarter CAR T therapy hits hard to tumors

“…Further improvement of transfection strategies is promising to overcome the barriers of the solid tumor microenvironment (TME). Hitherto we have reviewed some novel applications of nanotechnology in immunoengineering of CAR T cells (6), limitations and their possible solutions for improving different generations of CARs (7), and some novel approaches to enhance the efficacy of natural killer cells (NK) with CARs (8). Herein we discuss promising strategies to mitigate CAR T cell-related toxicities.…”