CAR T-cell therapy in hematologic and solid malignancies: mechanisms, clinical applications, and future directions

Chimeric antigen receptor (CAR) T-cell therapy represents a groundbreaking approach to treating malignancies. This immunotherapy involves genetic modification of T cells to target and eliminate tumor cells, proving effective across various cancers. Its remarkable specificity, solid tumor infiltration, and durable responses highlight its potential to revolutionize cancer treatment. By targeting specific tumor antigens, CAR-T-cell therapy minimizes off-target effects and enables personalized treatment. Six CAR-T-cell therapies have been authorized, showing exceptional effectiveness, particularly for B-cell malignancies and multiple myeloma. However, challenges such as cytokine-release syndrome, neurotoxicity, and difficulties in targeting solid tumors due to issues like unreliable antigens, hypoxic tumor cores, and immunosuppressive environments complicate its application. Addressing these requires innovative strategies to enhance CAR-T cell efficacy and reduce toxicity. This review details CAR T-cell engineering, signaling pathways, clinical successes in B-cell malignancies, challenges in solid tumors, emerging strategies, and safety management.