March 2nd, 2006
Micromet Study Provides New Insight into Dosing Requirements for Anti-Cancer Antibodies
March 2nd, 2006 – Munich, Germany – Micromet has published a study in the recent issue of Molecular Immunology (2006; 43: 1183-1193) (1) explaining why large amounts of antibodies are needed to achieve a therapeutic effect in cancer patients. Each treatment cycle requires substantial amounts of antibodies per patient – typically in the gram range – although such antibodies appear quite potent in cell culture experiments. Micromet researchers have now performed cell culture experiments in the presence of human serum investigating both trastuzumab (Herceptin®) and Micromet's human anti-Ep-CAM antibody adecatumumab (MT201). The latter is currently in two phase II studies for breast and prostate cancer, and is partnered with Serono. The study focused on antibody-dependent cellular cytotoxicity (ADCC), a mechanism by which antibodies recruit natural killer cells to tumor cells. According to recent studies (2-5), ADCC represents a key mode of action of trastuzumab as well as adecatumumab.
The newly published results demonstrate that ADCC of both antibodies is strongly inhibited by serum due to non-specific Immunoglobulin G (IgG) antibodies competing for binding of therapeutic antibodies to the Fc-gamma receptor III (CD16) on natural killer cells. In a physiological environment, the efficacy of therapeutic antibodies may therefore be primarily limited by their recruitment of natural killer cells rather than by their binding affinity to tumor cells.
"Our findings provide a simple explanation as to why monoclonal antibody therapies relying on ADCC are not as potent in man as they appear in cell culture systems. We show that high antibody doses are needed to make up for the inhibition by serum IgG although there are certainly further factors improving with high antibody doses, such as tumor penetration or complement activation. In order to assess antibody potency more realistically, we suggest to routinely test for ADCC in the presence of human serum," commented Patrick Baeuerle, Micromet's Chief Scientific Officer. "Moreover, these findings provide further evidence that adecatumumab could be comparable to trastuzumab in terms of anti-tumor mechanism and efficacy, in line with previously published results (6). However, we believe that adecatumumab may be applicable to the treatment of a broader segment of cancer patients, because the Ep-CAM target is more frequently expressed in human carcinomas than the target for trastuzumab."
In January 2006, Micromet announced a definitive agreement to merge with CancerVax Corporation (NASDAQ: CNVX) to create a transatlantic, NASDAQ-listed company with a highly differentiated drug development pipeline focused on oncology, autoimmune and inflammatory diseases, and a proprietary technology base for the development of antibody-based product candidates. The merger is subject to a number of conditions and is expected to close in the second quarter of 2006. Upon closing of the transaction, the Company's shares are expected to continue to trade on the NASDAQ National Market. CancerVax will be renamed "Micromet", Inc., and application will be made to NASDAQ to change the ticker symbol to "MITI". On February 13, 2006, CancerVax filed a registration statement on Form S-4 in connection with the transaction that contains a proxy statement/prospectus with the U.S. Securities and Exchange Commission. |
