Novel Approach to Interferon-Alpha Gene Therapy for Bladder Cancer in a Mouse Model

• Published in: Cancer biology & therapy 2004-10, Vol.3 (10), p.923-930
• Format: Article
• Language: English
• ISSN: 1538-4047; 1555-8576
• DOI: 10.4161/cbt.3.10.1231

Gene therapy that causes the bladder to act like a "bioreactor" to produce and secrete the anti-cancer agent interferon-alpha has shown dramatic benefits in preclinical tests, say researchers at The University of Texas M. D. Anderson Cancer Center. The researchers say their findings, published in the September issue of Molecular Therapy, suggest this gene therapy strategy holds much promise for treating aggressive human superficial bladder cancer and that a clinical trial is being planned. Human bladder tumors growing in experimental mice substantially decreased in size after two treatments with novel gene-based therapy. There was little or no evidence of cancer cells remaining in the bladder in many of the mice after treatment. Also, every kind of bladder cancer cell line tested in the laboratory responded, even cells known to be resistant to the interferon-alpha protein. "Of course these results have been achieved in mice, not humans, but they are very exciting," says the lead investigator William Benedict, M.D., professor in the Department of Genitourinary Medical Oncology. "I have never seen a potential therapy for superficial bladder cancer that could produce such marked regression of tumors within the bladder." Bladder cancer is the fifth leading U.S. cancer, and "superficial" bladder cancer -- cancer confined to the lining of the bladder wall -- is the most common type, with more than 45,000 new cases each year. Although some patients with this cancer can be cured with the standard biologic therapy, the use of BCG, tumors will reappear in about half of patients, and up to 30 percent of them will die from disease. Because neither BCG nor chemotherapy can effectively prevent a significant percentage of superficial bladder cancer from becoming aggressive, researchers at M. D. Anderson have been studying novel gene therapy approaches to this clinical problem. Their work is being funded by a $13 million Specialized Programs of Research Excellence (SPORE) grant awarded to M. D. Anderson by the National Cancer Institute in 2001 ¯ the only such federal SPORE dedicated to bladder research. The bladder has long been thought to be ideal target for gene therapy, because it is easily accessible by catheter, and is largely a self-contained "bag-like" organ. Benedict and his team of researchers decided to look at use of gene therapy to deliver interferon-alpha, an immune system modulator which can improve a patient's natural response against cancer as well as kill