Mesothelin (Region I) (MSLN)

Mesothelin is a 40 kDa glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that is overexpressed in several human malignancies, including mesothelioma and ovarian cancer, while maintaining restricted expression in normal mesothelial cells (UniProt P50607). Region I specifically refers to the N-terminal domain of the membrane-bound protein (residues 296–390), which serves as the essential binding site for MUC16 (CA125) (PubMed: 19147765). This biochemical interaction is a key driver in the peritoneal metastasis of ovarian cancer cells and the progression of malignant mesothelioma (PubMed: 17200345). Because Region I is highly accessible on the cell surface and contains the primary functional epitope for MUC16 binding, it is the preferred target for therapeutic monoclonal antibodies like amatuximab and various CAR-T cell therapies (PubMed: 24938305). Targeting this specific region allows for the dual benefit of blocking pro-metastatic signaling and directing potent cytotoxic payloads or immune effectors specifically to the tumor microenvironment (NCI, 2023).

Other names

MSLNCAK1 antigenPre-pro-megakaryocyte-potentiating factorMPFN-terminal mesothelin domain

Binding to the N-terminal Region I of mesothelin to competitively inhibit its interaction with MUC16 (CA125), thereby disrupting tumor cell adhesion and peritoneal spreading, or acting as a targeting moiety for the delivery of immunotoxins, antibody-drug conjugates, and chimeric antigen receptor (CAR) T-cells.