dnTGFβRII-M5

dnTGFβRII-M5 is an investigational second-generation chimeric antigen receptor (CAR) T-cell therapy designed to target mesothelin-expressing solid tumors. Developed at the University of Pennsylvania, the therapy is uniquely engineered to resist the immunosuppressive effects of transforming growth factor-beta (TGF-β) within the tumor microenvironment. It achieves this through the expression of a dominant-negative TGF-beta receptor II (dnTGFβRII), a truncated version of the receptor that lacks the intracellular signaling domain. This truncated receptor acts as a "sink" by binding and sequestering extracellular TGF-β, thereby preventing the induction of inhibitory pSMAD signaling within the CAR T cells and protecting them from TGF-β-mediated suppression. The construct utilizes the M5 single-chain variable fragment (scFv) for mesothelin recognition, paired with a 4-1BB (CD137) co-stimulatory domain and a CD3-zeta signaling chain.

Other names

dnTGFβRII-mesothelin CAR Tmesothelin-targeting dnTGFβRII CAR TCART-meso-dnTGFβRII