Mesothelin-targeting CAR-T cell therapy

MCAR-T refers to T cells genetically engineered to express a chimeric antigen receptor (CAR) targeting mesothelin (MSLN), a cell surface glycoprotein that is overexpressed in various aggressive solid tumors, including uterine endometrial carcinoma (UEC), ovarian cancer, mesothelioma, and pancreatic adenocarcinoma. The specific construct often referred to in research (such as the SS1-based CAR) typically utilizes an anti-MSLN single-chain variable fragment (scFv) fused to intracellular signaling domains, commonly including CD28 and/or 4-1BB costimulatory domains and the CD3ζ activation subunit. Upon binding to mesothelin on tumor cells, these engineered T cells undergo activation, proliferation, and release cytotoxic molecules like perforin and granzymes to induce tumor cell death. While MCAR-T has shown potent activity in preclinical models, its clinical efficacy in solid tumors has historically been challenged by poor tumor infiltration, the immunosuppressive nature of the tumor microenvironment, and potential antigen escape.

Other names

Mesothelin-directed chimeric antigen receptor T-cell therapyanti-mesothelin CAR-T cellsMSLN-targeting CAR-T