Engineering the next generation of CAR T- cells: precision modifications, logic gates and universal strategies to overcome exhaustion and tumor resistance

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape of hematologic malignancies, delivering durable remissions in diseases previously associated with poor outcomes. However, translating this success to solid tumors has proven challenging due to antigen heterogeneity, limited tumor infiltration, immunosuppressive tumor microenvironments, and progressive T-cell exhaustion. In response, next-generation CAR T-cell platforms have emerged that integrate advances in receptor architecture, intracellular signaling, and programmable control systems to enhance specificity, persistence, and safety. This review comprehensively examines recent innovations in CAR T-cell engineering,…