One Health in ACTION: Human Breast Cancer Comparative Medicine Research Advances at MD Anderson Cancer Center
Physicians, PhDs, and Veterinarians working collaboratively and synergistically
Department of Veterinary Sciences, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas
Provided September 13, 2010 by:
Christian R. Abee, DVM, MS, DACLAM
Doctor R. Lee Clark Professor and Chair
Department of Veterinary Sciences
Director, Michale E. Keeling Center for Comparative Medicine and Research
University of Texas MD Anderson Cancer Center
Bastrop, TX 78602
Telephone: (512) 321-3991
Research at the Keeling Center has led to discovery of new breast cancer therapeutic monoclonal antibodies, and the development of early breast cancer tests based on the antibodies. These antibodies were discovered in the laboratory of Keeling Center investigator Dr. Feng Wang-Johanning [MD, PhD] and her Keeling Center collaborator, Dr. Gary Johanning [PhD]. The monoclonal antibodies are directed against an ancient retrovirus that originated outside the human body as a remnant of an exogenous retrovirus, and subsequently became incorporated into the genome of primates millions of years ago. This retrovirus, termed human endogenous retrovirus (HERV), currently resides in the genome of all humans.
Dr. Wang-Johanning and Dr. Johanning are focusing their studies on one highly active subgroup of HERV, HERV type K. HERV-K is not usually expressed in normal, non-cancer cells, but they found that its expression re-emerges in human breast cancer, making it a good target for antibody therapy. Dr. Wang-Johanning’s major research discovery to date is that monoclonal and single chain antibodies against HERV-K are effective in inhibiting breast cancer cell proliferation and inducing cell cycle arrest and apoptosis, both in vitro and in vivo. Pivotal studies in immunodeficient mice demonstrated that tumor sizes were significantly reduced, and onset of tumorigenesis was significantly delayed, in antibody-treated mice bearing breast tumors.
HERV-K is thus a novel antigen target for breast cancer, and Dr. Wang-Johanning’s pre-clinical studies provide compelling evidence that antibodies to HERV-K have the potential to be effective therapeutic agents for treating breast cancer. She is currently developing humanized and human antibodies for clinical trials, aimed at translating her laboratory results to breast cancer patients. Drs. Wang-Johanning and Johanning are hopeful that this antibody will rival the effectiveness of the well-known breast cancer therapeutic antibody Herceptin. There is reason for their optimism, because while Herceptin is effective against only 25-30 percent of breast cancers, anti-HERV-K antibodies have the potential to be effective against almost all human breast cancers.
The research of Dr. Wang-Johanning and collaborators has just taken an exciting turn. They are taking advantage of the presence of HERV-K in breast cancer to develop early breast cancer tests. These tests are based on detection of anti-HERV-K serum antibodies and viral RNA, and will be analogous to the PSA test that is widely used for prostate cancer screening. There is a need for these tests, because currently there are no sensitive and specific serum tests for breast cancer.
These discoveries would not have been possible without “One Health” collaboration between Dr. Wang-Johanning’s group and investigators at the main M. D. Anderson Cancer Center campus in Houston. Kelly Hunt, MD, breast cancer surgeon, provided breast cancer serum and tumor tissues for Dr. Wang-Johanning’s projects. In addition, Stephan Ambs, PhD, National Cancer Institute, is collaborating with Dr. Wang-Johanning’s laboratory to assess the clinical significance of elevated HERV-K in breast cancer. Bruce Bernacky, DVM at the Keeling Center, will also play a prominent role in upcoming studies with Dr. Wang-Johanning because he will provide access to primates for testing her antibodies prior to human clinical trials.
Note: Please see the current issue of the Institute of Laboratory Animal Research (ILAR) Journal which contains “One Health: The Intersection of Humans, Animals and the Environment – Scientific Editor: James G. Fox, DVM, MS [2010 Volume 51, Number 3]
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