Anti-Human Mesothelin (Amatuximab) (M1430-GRP)

Mesothelin is involved in normal cell adhesion, differentiation, and signal transduction processes1. In cancer, mesothelin is involved in proliferation, cell migration, and inhibition of apoptosis, making mesothelin a target for cancer therapy. Mesothelin binds to the cancer antigen MUC16 (CA-125), and this interaction may promote cell adhesion and metastasis. MORAb-009 (Amatuximab) was generated by panning a phage display library created by immunizing a mouse with mesothelin cDNA on mesothelin-positive cells2,3. A mouse precursor antibody was identified, isolated, and its affinity optimized by engineering its variable regions to derive SS1 (scFV). The gene encoding mesothelin Fv (SS1 scFv) was then fused with human IgG1 and kappa regions to form a chimeric antibody. Amatuximab binds mesothelin on the cell surface of ovarian, mesothelioma, and pancreatic cancer cell lines2. Amatuximab also stains neoplastic cells using immunohistochemistry techniques. Amatuximab is internalized upon binding mesothelin at the cell surface. Additionally, amatuximab enhances antibody-dependent cytotoxicity in mesothelin positive cancer cell lines and inhibits interaction of mesothelin-expressing cells with MUC16-expressing cells. Preliminary epitope mapping shows that Amatuximab binds mesothelin at its amino terminus.