Clinical Translation of CAR-T Therapy in Hematologic Ocologyr

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies by reprogramming a patient's T cells to target tumor-specific antigens. Despite great success in clinical care, challenges such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), neurotoxicity, and limited efficacy in solid tumors remain. Recent advances in CAR-T engineering-including dual-targeted CARs, armored CARs with cytokine-secreting capabilities, and safety switches-have enhanced tumor specificity, reduced off-target effects and improved durability. However, the immunosuppressive tumor microenvironment (TME) in solid tumors remains a key obstacle that affects the infiltration, activation, and long-term function of CAR-T cells. This review systematically analyzes the clinical translation of CAR-T therapies, focusing on their mechanism of action, efficacy in hematological and solid tumors, and management of adverse effects. We highlight the efficacy and toxicity profiles of CAR-T and summarize relevant emerging strategies such as CAR T cell therapy in combination with other immunotherapies such as checkpoint inhibitors. Our findings emphasize that CAR-T therapies are transitioning from a salvage option to a first-line contender for hematologic cancers, but their broader application will need to address durability and safety trade-offs. Future research should prioritize multifunctional CAR designs, predictive biomarkers of toxicity, and personalized manufacturing protocols to expand its accessibility. Overcoming these challenges will make CAR-T more dominant in solid and refractory cancers and bring hope to more cancer patients.