Revolutionizing CAR-T Therapy: The CTLA-4 Tail Fusion Advantage

Chimeric antigen receptor (CAR)-T cells, although potent therapeutics, often face significant challenges in achieving their full efficacy. In this study, it is stated that the endocytic capability of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) cytoplasmic tail to revamp CAR functionality and significantly bolsters CAR-T cell effectiveness in live subjects. The molecular dynamics of reengineered CAR with CCT fusion results in reduced CAR-mediated trogocytosis, loss of tumor antigen and improved CAR-T survival. CARs with either monomeric (CAR-1CCT) or duplex CCTs (CAR-2CCT) have superior antitumor efficacy in a relapsed leukemia model.

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