GPC3-SynNotch-S-CAR T cells

GPC3-SynNotch-S-CAR T cells are an investigational, logic-gated chimeric antigen receptor (CAR) T-cell therapy designed to target hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC) [1230]. Developed by SCG Cell Therapy in collaboration with the Technical University of Munich and Helmholtz Munich, this therapy utilizes a synthetic Notch (SynNotch) logic-gate system to enhance specificity and prevent off-target toxicities [1230]. The SynNotch receptor is engineered to recognize glypican-3 (GPC3), a tumor-associated antigen highly expressed in HCC, as a gating signal [1230]. Upon binding to GPC3, the SynNotch receptor undergoes cleavage, releasing a transcription factor that drives the expression of a second-generation CAR (S-CAR) targeting the HBV envelope protein (HBVenv) on the surface of infected or malignant cells [1230]. This "IF-THEN" logic circuit ensures that the CAR-T cells are only activated and exert cytotoxic activity in the presence of both GPC3 and HBVenv, preventing unwanted activation by circulating soluble hepatitis B surface antigen (HBsAg) and minimizing off-tumor toxicity [1230].

Other names

GPC3-SynNotch-S-CAR T-cellsGPC-3-SynNotch-S-CAR T-cellsGPC 3-SynNotch-S-CAR T-cellsGPC3-SynNotch-S-CAR-T cellsGPC-3-SynNotch-S-CAR-T cellsGPC 3-SynNotch-S-CAR-T cells