VHH-based Claudin 18.2 CAR T-cell

VHH-based Claudin 18.2 CAR T-cell is an investigational chimeric antigen receptor (CAR) T-cell therapy utilizing a nanobody (VHH) or variable heavy-chain domain to target Claudin 18.2 (CLDN18.2), a protein frequently overexpressed in gastrointestinal (GI) malignancies. Developed by researchers at the Mayo Clinic, this therapy aims to provide superior specificity and efficacy compared to traditional single-chain variable fragment (scFv)-based CARs. Preclinical studies in gastric and colorectal cancer models have demonstrated significant antitumor activity and reduced off-tumor toxicity. An advanced iteration of this platform incorporates a synNotch inducible system that enables the conditional targeting of Fibroblast Activation Protein (FAP) on cancer-associated fibroblasts (CAFs) only upon engagement with Claudin 18.2-positive tumor cells. This dual-targeting approach is designed to remodel the immunosuppressive tumor microenvironment into an immune-permissive state, potentially improving clinical outcomes in refractory solid tumors such as gastric, pancreatic, and colon cancers.

Other names

VHH Claudin 18.2 CARTnanobody-based Claudin 18.2 CAR T-cellvariable heavy-chain domain claudin 18.2 CAR T-cellinducible Claudin 18.2/FAP dual-targeting CART