Systematic Engineering of TROP2-Targeted CAR T-Cell Therapy Overcomes Resistance Pathways in Solid Tumors.

ABSTRACT: Antibody-based therapies have revolutionized cancer treatment but have several limitations. These include downregulation of the target antigen, mutation of the target epitope, and, in the case of antibody-drug conjugates (ADC), resistance to the chemotherapy warhead. As TROP2-targeted therapy with ADCs yields responses in TROP2+ solid tumors, but the responses lack the durability observed with other immunotherapy-based approaches, we developed TROP2-targeting chimeric antigen receptor (CAR) T cells as an alternative. The TROP2-directed CAR T cells showed high potency against multiple solid tumor models. Moreover, TROP2-directed CAR T-cell therapy preserved high potency in models of ADC resistance and could be further engineered to prevent cell therapy resistance. This was achieved by lever

SUBMITTER: Brea EJ 

PROVIDER: S-EPMC12580781 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature