Efficacy, Safety, and Challenges of CAR T-Cells in the Treatment of Solid Tumors

SIMPLE SUMMARY: Chimeric antigen receptor T cells (CAR T-cells) are engineered T cells that target tumor-associated antigens. CAR T-cell therapy is a novel developed immunotherapy initially for destroying hematological malignancies. Its great success in clinical practice of hematological malignancies encourages oncologists and scientists to use CAR T-cells for the treatment of solid cancers. However, the efficacy of CAR T-cells in solid tumors is not as good as expected in hematological malignancies. In this review, we summarized the efficacy, safety, and challenges of CAR T-cell therapy in the clinical management of solid tumors. We also discussed the potential strategies currently applied to improve the efficacy and safety of CAR T-cell therapy in solid tumors, and finally prospected the future study direction for CAR T-cell therapy. ABSTRACT: Immunotherapy has been the fifth pillar of cancer treatment in the past decade. Chimeric antigen receptor (CAR) T-cell therapy is a newly designed adoptive immunotherapy that is able to target and further eliminate cancer cells by engaging with MHC-independent tumor-antigens. CAR T-cell therapy has exhibited conspicuous clinical efficacy in hematological malignancies, but more than half of patients will relapse. Of note, the efficacy of CAR T-cell therapy has been even more disappointing in solid tumors. These challenges mainly include (1) the failures of CAR T-cells to treat highly heterogeneous solid tumors due to the difficulty in identifying unique tumor antigen targets, (2) the expression of target antigens in non-cancer cells, (3) the inability of CAR T-cells to effectively infiltrate solid tumors, (4) the short lifespan and lack of persistence of CAR T-cells, and (5) cytokine release syndrome and neurotoxicity. In combination with these characteristics, the ideal CAR T-cell therapy for solid tumors should maintain adequate T-cell response over a long term while sparing healthy tissues. This article reviewed the status, clinical application, efficacy, safety, and challenges of CAR T-cell therapies, as well as the latest progress of CAR T-cell therapies for solid tumors. In addition, the potential strategies to improve the efficacy of CAR T-cells and prevent side effects in solid tumors were also explored.