February 3rd, 2006
New Study Supports Ep-CAM as Prime Target for Antibody Therapy in Common Cancers
Ep-CAM Is Frequently Expressed in Colon, Lung, Prostate and Gastric Cancers
February 3, 2006 – Munich, Germany – The University of Basel, Switzerland, and Micromet AG have published a new study on the frequent high-level expression of antibody target epithelial cell adhesion molecule (Ep-CAM) in colon, lung, prostate and gastric cancers. The report has been published in the British Journal of Cancer (2006, 94: 128 – 135) (1). Ep-CAM is the target for Micromet's human antibody adecatumumab (MT201), which currently is in two phase II clinical trials in prostate and metastatic breast cancer, and is partnered with Serono.
The immunohistochemical study analyzed Ep-CAM expression on tissue micro-array samples from more than 4,000 cancer patients. Patient samples were derived from primary tumor tissues covering all stages, grades and histologies of respective cancer indications. High-level Ep-CAM expression, i.e. an intense and homogenous staining of tumor cells was observed for 97.7% of colon, 63.9% of lung, 87.2% of prostate and 90.7% of gastric cancer patients.
"Through its scientific co-founder Gert Riethmuller of Munich University, Micromet has a long-standing expertise and interest in Ep-CAM as a target for antibody-based therapeutics. Our data strongly support the notion that Ep-CAM is a prime target for immunotherapy", comments Patrick Baeuerle, Micromet's Chief Scientific Officer. "Together with data published earlier on breast cancer, our study suggests that a large percentage of patients with colon, lung, prostate, gastric and breast cancer may qualify for treatment with Ep-CAM-directed antibody therapies, such as adecatumumab. Therefore, we expect that at least five of the most frequent human malignancies can potentially be addressed by our product candidate."
Recently published studies support that over expression of Ep-CAM plays a pivotal role in tumorigenesis. In human breast cancer, over expression of Ep-CAM is a negative and independent prognostic marker for overall survival (2), and Ep-CAM is expressed significantly higher on metastatic than on primary breast tumors (3). Proliferation, migration and invasiveness of tumor cells is inhibited when Ep-CAM expression in breast cancer cell lines is reduced by a specific small inhibitory RNA (4). When over expressed in quiescent cells, Ep-CAM behaves like a classical oncogene, enabling growth of cells in soft agar and independence on serum growth factors (5). Lastly, highly tumorigenic human breast cancer stem cells are characterized by expression of Ep-CAM (ESA) (6).
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 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 as Micromet, Inc., and application will be made to NASDAQ to change the ticker symbol to "MITI". CancerVax expects to file a Form S-4 and related proxy statement/prospectus with the U.S. Securities and Exchange Commission and any other necessary government filings in the coming weeks. ###
Contact
Media: Evelyn Wolf
Phone: +49 89 895277-220, Email: evelyn.wolf@micromet.de
Investors: Ines-Regina Buth
Phone: +49 89 895277-221, Email: ines-regina.buth@micromet.de
References
(1) Went P, Vasei M, Bubendorf L, Terracciano L, Tornillo L, Riede U, Kononen J, Simon R, Sauter G, Baeuerle PA (2006). Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers, Brit J Cancer 94: 128-35.
(2) Spizzo G, Went P, Dirnhofer S, Obrist P, Simon R, Spichtin H, Maurer R, Metzger U, von Castelberg B, Bart R, Stopatschinskaya S, Kochli OR, Haas P, Mross F, Zuber M, Dietrich H, Bischoff S, Mirlacher M, Sauter G, Gastl G (2004). High Ep-CAM expression is associated with poor prognosis in node-positive breast cancer. Breast Cancer Res Treat 86: 207-13.
(3) Rao CG, Chianese D, Doyle GV, Miller MC, Russell T, Sanders Jr RA, Terstappen LWMM (2005). Expression of epithelial cell adhesion molecule in carcinoma cells in blood and primary and metastatic tumors. Intl J Oncol 27: 49-57.
(4) Osta WA, Chen Y, Mikhitarian K, Mitas M, Salem M, Hannun YA, Cole DJ, Gillanders WE (2004). Ep-CAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res 64: 5818-24.
(5) Munz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O (2004). The carcinoma-associated antigen Ep-CAM upregulates c-myc and induces cell proliferation. Oncogene 23: 5748-58.
(6) Al-Hajj W, Micha M, Benito-Hernandez A, Morrison SJ, Clarke MF (2003). Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100: 3983-8. |
