Supercharging the metabolic engine: mitochondrial engineering strategies for CAR-T persistence in solid tumors

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in hematological malignancies, yet its efficacy in solid tumors is severely limited by the metabolically hostile tumor microenvironment (TME). Within this landscape, CAR-T cells undergo rapid functional exhaustion driven by mitochondrial dysfunction and metabolic insufficiency. This mini-review synthesizes emerging mitochondrial engineering strategies designed to restore metabolic fitness and persistence. We first exa