mesothelin-targeted CAR T-cell therapy

MSLN-targeted CAR T-cell therapy is an autologous adoptive cell immunotherapy designed to treat mesothelin-expressing solid tumors. Mesothelin (MSLN) is a cell-surface glycoprotein overexpressed in various cancers, including mesothelioma, pancreatic, ovarian, and lung adenocarcinoma, while maintaining limited expression in normal mesothelial tissues. The therapy involves genetically engineering a patient's T cells to express a chimeric antigen receptor (CAR) that typically consists of an anti-MSLN single-chain variable fragment (scFv) linked to intracellular signaling domains such as CD3-zeta and costimulatory domains like 4-1BB or CD28. Upon infusion, these engineered cells recognize and bind to MSLN on tumor cells, leading to T-cell activation and cytotoxic tumor cell killing. Advanced iterations include logic-gated constructs (e.g., A2 Biotherapeutics' Tmod platform) to enhance tumor specificity by targeting cells with HLA loss of heterozygosity, or the incorporation of checkpoint blockade components like anti-PD-1 to resist the immunosuppressive tumor microenvironment.

Other names

CAR T-cell therapy (MSLN-targeted)MSLN CAR-Tanti-MSLN CAR-Tmesothelin-targeted chimeric antigen receptor T-cell therapy