Antibody based EpCAM targeted Therapy of Cancer, Review and update.

Abstract

Todays, after four decades of the discovery of monoclonal antibodies by Kohler and Milstein in 1975, a dozen of antibodies are used in cancer targeted therapy with different strategies. The success of these antibodies depends on the specificity of antigens expressed on the cancer cells. Epithelial cell adhesion molecule (EpCAM), a homophilic cell-cell adhesion glycoprotein is a well- known tumor antigen, which expresses on epithelial tumors and circulating tumor cells as well as cancer stem cells. The EpCAM signaling pathway is associated with proliferation, differentiation and adhesion of epithelial cancer cells. Here we review EpCAM structure, expression profile and its signaling pathway in cancer cells. In addition, we focused on structure, mechanism of action and success of anti EpCAM antibodies which have been used in different clinical trials. Based on literatures, Edrecolomab show limited efficacy in the phase III studies. The wholly monoclonal antibody Adecatumumab is dose- and target-dependent in metastatic breast cancer patients expressing EpCAM. The chimeric antibody Catumaxomab is approved for the treatment of malignant ascites; however, this Mab showed considerable results in intrapleural administration in cancer patients. Anti EpCAM toxin conjugated antibodies Oportuzumab Monatox (scFv antibody and Pseudomonas exotoxin A (ETA)) and Citatuzumab Bogatox (Fab fragment with bouganin toxin) and also, immono-conjugate antibody Tucotuzumab (wholly monoclonal antibody with IL2), shown acceptable results in different clinical trials. Almost, all of the antibodies were well- tolerated; however, still more clinical trials are needed for approval of the antibodies for treatment of specific tumors.