aMSLN-28BBZ

aMSLN-28BBZ is a third-generation chimeric antigen receptor (CAR) T-cell therapy designed to target mesothelin (MSLN), a cell-surface glycoprotein frequently overexpressed in solid tumors such as pancreatic cancer. The "28BBZ" nomenclature indicates that the CAR construct incorporates both CD28 and 4-1BB (CD137) costimulatory domains in tandem with the CD3ζ signaling domain. This configuration is intended to optimize T-cell activation, metabolic fitness, and long-term persistence compared to first- or second-generation constructs. In preclinical research conducted by WuXi AppTec, aMSLN-28BBZ demonstrated potent short-term cytotoxicity and cytokine secretion against mesothelin-positive tumor cells. However, its efficacy was found to be limited by PD-L1-mediated immunosuppression in the tumor microenvironment, leading to the development of "armored" variants like aMSLN-28BBZ-mPD-1, which co-express a membrane-bound PD-1 antibody to block inhibitory signaling.

Other names

anti-MSLN-28BBZ CAR-Tanti-MSLN28BBZ CAR-Tanti-MSLN 28BBZ CAR-Tmesothelin-targeted CAR-T