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aMSLN-28BBZ-mPD-1 is an armored chimeric antigen receptor (CAR) T-cell therapy designed to target mesothelin (MSLN) while simultaneously expressing a membrane-bound PD-1 receptor (mPD-1). Developed by WuXi AppTec, this third-generation CAR-T construct incorporates CD28 and 4-1BB costimulatory domains alongside the CD3ζ signaling domain. The inclusion of the membrane-bound PD-1 receptor serves as a checkpoint blockade mechanism, effectively sequestering PD-L1 within the tumor microenvironment to prevent the inhibition of CAR-T cell activity via the PD-1 pathway. This strategy aims to overcome the immunosuppressive nature of solid tumors, particularly pancreatic cancer, by enhancing CAR-T cell infiltration and long-term cytotoxicity.
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