Human-centric preclinical models for CAR T cell therapy in solid tumors: Where patient-derived organoids fit

Chimeric antigen receptor (CAR) T cell therapy has shown promising activity in solid tumors, yet translational progress remains limited by preclinical models that incompletely capture human tumor biology. Patient-derived organoids (PDOs) preserve key features of human tumors, including cellular heterogeneity and tissue architecture, thereby enabling functional evaluation of CAR T cell targets, next-generation approaches, resistance mechanisms, and selected safety considerations. We discuss how PDOs complement existing preclinical platforms to support CAR T cell development for solid tumors.