Mesothelin (MSLN) (MSLN)

Mesothelin is a 40-kDa glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that is normally expressed at low levels on the mesothelial cells of the pleura, peritoneum, and pericardium (UniProt Q13421). It is significantly overexpressed in several human tumors, most notably malignant mesothelioma, ovarian cancer, and pancreatic adenocarcinoma, making it a prominent target for cancer immunotherapy (PMID: 27503109). The physiological function of mesothelin remains largely unknown, though it is known to bind to CA-125 (MUC16), a protein involved in cell adhesion. This interaction suggests a role in the metastatic spread of tumors within the abdominal cavity (PMID: 15374955). Therapeutic strategies targeting mesothelin include monoclonal antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR) T-cell therapies (PMID: 30552133). Clinical challenges include the potential for on-target off-tumor toxicity against normal mesothelial tissues and the shedding of mesothelin into the circulation. Shed mesothelin can act as a decoy for therapeutic agents, potentially reducing efficacy (PMID: 24510957). Despite these challenges, mesothelin remains a highly prioritized target due to its limited expression in normal tissues and high prevalence in aggressive cancers.

Other names

MSLNCAK1 antigenPre-pro-megakaryocyte-potentiating factorMPFSMRP

Targeting of mesothelin-expressing cells via antibody-dependent cellular cytotoxicity (ADCC), delivery of cytotoxic payloads through antibody-drug conjugates (ADCs), or direct T-cell mediated killing using CAR-T or TCR-T therapies.