Anti-Mesothelin Monoclonal Antibody (Anetumab)

Mesothelin is a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein encoded by the MSLN gene. In normal human tissues, it is mainly expressed on the surface of mesothelial cells lining the pleura, pericardium, and peritoneum, but shows marked overexpression in various malignancies, including malignant mesothelioma, pancreatic cancer, ovarian cancer, and lung adenocarcinoma. The protein precursor undergoes proteolytic cleavage to generate a 30 kDa membrane-bound fragment (the mature mesothelin) and a 31 kDa shed form known as megakaryocyte-potentiating factor (MPF). Through specific interactions with cell surface adhesion molecules such as CA125 (MUC16), mesothelin participates in regulating cell adhesion, survival, and metastasis, playing a particularly critical role in tumor cell peritoneal implantation and invasion. Due to its highly restricted expression in normal tissues but widespread upregulation in tumors, mesothelin has emerged as a highly promising tumor-specific therapeutic target. Currently, multiple mesothelin-targeted strategies are under active development, including antibody-drug conjugates, chimeric antigen receptor T-cell therapy (CAR-T), immunotoxins, and cancer vaccines, some of which have shown preliminary efficacy in clinical trials for mesothelioma, pancreatic cancer, and ovarian cancer.