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Mesothelin is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that is normally expressed at low levels on mesothelial cells lining the pleura, peritoneum, and pericardium (UniProt Q61468). In Mus musculus, the protein is encoded by the Msln gene and is processed from a 71 kDa precursor into a 31 kDa secreted fragment known as megakaryocyte-potentiating factor (MPF) and a 40 kDa membrane-bound mature mesothelin (NCBI Gene: 56047). While its exact physiological function remains elusive, it is hypothesized to play a role in cell adhesion and signaling, particularly through its interaction with MUC16 (CA125) (PubMed: 15310686). Mesothelin is highly overexpressed in several human malignancies, including mesothelioma, pancreatic, and ovarian cancers, making it a prominent target for immunotherapy (PubMed: 17005656). In preclinical research, mouse mesothelin is frequently studied to evaluate the efficacy and safety of mesothelin-targeted therapies, such as CAR T-cells and antibody-drug conjugates, using syngeneic mouse models (PubMed: 28235901). These therapeutic strategies aim to exploit the high tumor-to-normal tissue expression ratio to achieve selective anti-tumor activity while monitoring for potential on-target off-tumor toxicities in serosal tissues.
Binding to cell-surface mesothelin to facilitate immune-mediated lysis (via CAR-T or ADCC) or to deliver cytotoxic payloads (via ADCs), thereby inducing apoptosis in overexpressing tumor cells.
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