STEAP Antigen Provides Promising Route for New Therapies, PNAS Reports
Santa Monica, CA, December 7, 1999 - UroGenesys, Inc. today reported the discovery of a novel gene that provides a promising route for developing new therapies to treat prostate cancer. The studies, published today in the journal Proceedings of the National Academy of Sciences (PNAS), describe a novel cell-surface antigen called STEAP which is expressed at high levels on prostate cancers, but is rarely produced in non-prostate tissues. These results indicate that the STEAP molecule may have utility as a target for new prostate cancer therapies, as well as for improved diagnostic tools to help monitor progression of the disease.
"STEAP possesses several features that make it a promising target for new cancer treatments," said Aya Jakobovits, Ph.D., Vice President of Research and Chief Scientific Officer at UroGenesys and an author on the paper. "The antigen is expressed at high levels on prostate tumors throughout all stages of the disease, including metastatic tumors. Its prostate-specific expression suggests that drugs targeted to STEAP may have a favorable safety profile."
Dr. Jakobovits continued, "STEAP is also expressed in androgen-independent tumors, providing an avenue for treatment of cancers that have become resistant to conventional hormone ablation therapies. Its presence on the surface of prostate cancer cells makes the molecule suitable for a wide variety of therapeutic approaches, including antibodies, small molecules and vaccines."
"STEAP is the first antigen to emerge from UroGenesys' in-house discovery program," said Donald B. Rice, Ph.D., President and Chief Executive Officer of UroGenesys. "The discovery illustrates how our disease-focused genomics program positions UroGenesys to identify and advance the development of products that may lead to improved treatments for prostate and other cancers." Dr. Rice added that UroGenesys plans to accelerate the development of new therapeutic and diagnostic products based on its proprietary antigens primarily through strategic alliances with pharmaceutical and biotechnology companies, while pursuing selected clinical developments separately. Study Results Researchers at UroGenesys identified the STEAP gene by comparing RNA sequences isolated from patient-derived specimens of prostate cancer to sequences isolated from benign prostatic tissues. Once they had successfully cloned STEAP (named for Six-Transmembrane Epithelial Antigen of the Prostate), the UroGenesys team looked for its presence in a wide variety of normal and diseased tissues. The researchers confirmed high cell-surface expression of STEAP in all human prostate cancer samples tested, and further showed that expression of the protein was restricted predominantly to the prostate among normal body tissues. Studies of STEAP¹s structure and localization to the cell surface imply its function as an ion channel or transport protein.
Key to the STEAP gene discovery was UroGenesys' use of its proprietary xenograft mouse models that mimic the progression of advanced prostate cancer in humans, including the development of metastatic and hormone refractory disease. By implanting patient-derived tumor samples into immune-deficient mice, the Company is also able to generate a renewable supply of primary and metastatic tissues that are otherwise difficult to obtain. UroGenesys utilizes these tissues in its gene discovery and validation programs.
"Use of these xenografts is critical to the discovery of clinically-relevant targets that are uniquely expressed in prostate tumors and other cancers," noted Dr. Jakobovits. "Applying this tool together with our target validation expertise has already led to the discovery of over 30 additional new antigens implicated in prostate cancer."
Background on Prostate Cancer
Prostate cancer, which accounts for about 40 percent of all male cancers, is currently the most common type of cancer in American men and the second leading cause of cancer-related death in this population. An estimated 180,000 new cases of prostate cancer are diagnosed each year in the United States, and approximately 40,000 American men die of the disease annually. These numbers are expected to rise as the U.S. population experiences an increasing number of men entering their senior years, when most prostate cancers are diagnosed.
These figures underscore the need for new therapeutic approaches, particularly for metastatic and androgen-independent disease. To date, few targets that are specific to prostate cancer and are cell surface antigens have been discovered.
UroGenesys, Inc. is a privately held biotechnology company engaged in the development of innovative products for the treatment and diagnosis of urological diseases, with an initial emphasis on prostate cancer. UroGenesys, which began operations in 1997, was founded by leading cancer researchers and clinicians from the University of California, Los Angeles (UCLA) together with Donald B. Rice, Ph.D., an experienced business executive. The Company's laboratories and offices are located in Santa Monica, CA.
A backgrounder with additional information on UroGenesys, Inc. is available upon request.
Contacts:
Donald Rice, Ph.D.
Robert Gottlieb
President and CEO
Sharon Karlsberg
Aya Jakobovits, Ph.D. Feinstein Kean Healthcare Vice President, 617-577-8110
Research & CSO www.fkhealth.com
UroGenesys, Inc.
310-820-8029
www.urogenesys.com
Journal
Proceedings of the National Academy of Sciences