Strategies to Enhance CAR ‐T Cell Persistence in Hematologic Malignancies: From Molecular Design to Clinical Optimization

ABSTRACT Chimeric antigen receptor T (CAR‐T) cell therapy has demonstrated remarkable clinical efficacy in treating hematological malignancies. Nevertheless, the limited persistence of CAR‐T cells in vivo remains a major therapeutic hurdle, leading to disease relapse. This review examines current strategies to enhance CAR‐T cell durability, focusing on recent advances in CAR structural design, gene editing techniques, ex vivo culture optimization, clinical management approaches, and in vivo preparation. By integrating insights from preclinical studies and clinical trials, we provide a comprehensive analysis of methods to prolong CAR‐T cell persistence from a technical perspective and discuss future directions.