On the notion of synergy of monoclonal antibodies as drugs

Abstract

ErbB-2/HER2 is a member of the epidermal growth factor receptor (EGFR) family and when trans-activated, it stimulates several downstream signaling cascades, including the mitogen-activated protein kinase cascade. This ligand-less receptor is moderately expressed in normal adult tissues, where it regulates cell growth and differentiation, but gene amplification and consequent overexpression of the HER2/ErbB-2 protein have been associated with tumors of the breast and ovary, enhanced metastatic potential and poor prognosis. Monoclonal antibodies (mAbs) to ErbB-2/HER2 prolong survival of cancer patients, especially when combined with cytotoxic therapies. However, low effectiveness of therapeutic mAbs and the evolution of patient resistance call for further exploitation of the potential of mAbs. We found that combinations of anti-ErbB-2 mAbs comprising an antibody reactive with the dimerization site of ErbB-2 and an antibody recognizing another distinct epitope form an efficient and synergistic inhibitory system against an ErbB-2-overexpressing tumor.

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