Prostate Tumor Targeting and Killing Mechanisms by Salmonella typhimurium in the Mouse Model

8/27/2007

Prostate cancer occurs in a latent or clinical form in 30-40% of men by age 40-50, increasing substantially in men over 50 years of age. Current use of drugs and radiation has been partially effective only when the cancer is diagnosed early. Thus, research is needed into novel approaches to cure this devastating disease. The Cancer Research Center’s (CRC) novel approach utilizes a therapeutic strain of Salmonella typhimurium (CRC2631) to selectively target and destroy prostate tumor cells. Our first step was to demonstrate that CRC2631 was an attenuated strain with no harmful effects. Through painstaking genetic manipulation we have developed a Salmonella strain that is attenuated (non-toxic) and fails to show any adverse reaction when as many as 200 million (2×108) live bacteria are injected into a battery of mice. We now seek “seed money” to take the next step: to demonstrate that our therapeutic candidate Salmonella CRC2631 will reduce the size of prostate tumors and extend life expectancy. CRC is ready to embark on the testing of our therapeutic strain in mice genetically predisposed to prostate cancer (TRAMP mice). These mice typically die of prostate cancer at one year of age; the normal life expectancy of a laboratory mouse is two years. Although other investigators are also pursuing the use of Salmonella for therapy, our research has shown that our genetically modified strain is devoid of toxicity and has different affinities for tumor cells. Our next experiments are designed to answer the following questions: How much CRC2631 is required to successfully invade, inhibit and destroy primary and secondary prostate tumors in the TRAMP mouse model without ill effects to the mouse? Secondly, what Salmonella administration protocol is most effective at eliminating tumors and/or increasing the lifespan of TRAMP mice? We are optimistic that this animal model research will ultimately lead to an effective therapeutic treatment with Salmonella that will selectively target and eliminate prostate cancer. Upon completion of tests with the TRAMP mice, we will use the data from these animal model tests to apply for funds from cancer agencies to utilize this novel anti-cancer therapy in higher animals and eventually clinical trials in humans.

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