Bispecific Antibody MDX-210 for Treatment of Advanced Ovarian and Breast Cancer

A large number of monoclonal antibodies (MAbs) to various tumor cell lines have been developed (1 ). However, MAbs have thus far had limited therapeutic impact in oncology, probably in part because many murine MAbs do not effectively recruit immune effector mechanisms, such as complement fixation and antibody-dependent cell-mediated cytotoxicity (ADCC) in humans. Additionally, although humanized MAbs are being developed, when used therapeutically their immunological effectiveness may be limited by high concentrations of nonspecific immunoglobulin (Ig) in patient serum. These nonspecific Ig will compete with conventional MAbs for binding to Type I Fc receptors (FcγRI) on immune effector cells, and may therefore limit conventional MAbs ability to recruit an immune response. Recently, however, clinical efficacy of a humanized MAb directed against HER- 2/neu in patients with advanced breast cancer has been demonstrated (2 -4 ). Preclinical data suggests that mechanistically this activity may be as a consequence of modulation of important biologic properties of the HER- 2/neu receptor itself, as opposed to through an immunologic mechanism of tumor cell destruction.