Anti-Mesothelin Antibody (Anetumab)
Mesothelin is a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein encoded by the human MSLN gene. It is mainly expressed on the surface of mesothelial cells in the pleura, peritoneum, and pericardium, and is involved in processes such as cell–cell adhesion, signal transduction, and proliferation. In normal tissues, mesothelin expression is limited; however, in various malignant tumors—such as in more than 90% of malignant pleural mesotheliomas, most pancreatic ductal adenocarcinomas, ovarian cancers, as well as a subset of lung cancers and cholangiocarcinomas—mesothelin is markedly overexpressed and is therefore regarded as a highly promising tumor-specific target.
Anetumab is a humanized IgG1 monoclonal antibody directed against human mesothelin, derived from a mouse antibody through humanization. It has the typical full-length IgG1 structure, consisting of two heavy chains and two light chains. The antibody binds with high affinity and specificity to mesothelin on the surface of tumor cells via its Fab fragment, while its Fc fragment is of human IgG1 isotype and can potentially mediate effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In clinical studies, Anetumab is mainly used as an antitumor targeted therapeutic antibody, particularly for solid tumors with high mesothelin expression, such as malignant mesothelioma, ovarian cancer, and pancreatic cancer. In addition, Anetumab is often used as the antibody component in constructing antibody–drug conjugates (ADCs), such as Anetumab ravtansine (F1558) and Anetumab-MMAE (F1559), to deliver cytotoxic agents in a targeted manner, thereby achieving selective killing and precise treatment of mesothelin-positive tumor cells.