IDO Inhibitors for Combination Therapy of Prostate Cancer
Final rept. 15 Oct 2004-14 Oct 2005
LANKENAU INST OF MEDICAL RESEARCH WYNNEWOOD PA
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Cancer cells evade immunity during malignant progression. Thus strategies to reverse this process could offer new therapeutic options. Over expression of indoleamine 2,3-dioxygenase IDO in cancer cells inhibits T cell activation by tumor antigens. Notably combining an IDO inhibitor with cytotoxic drugs such as paclitaxel strongly and safely enhances antitumor efficacy in animal models of breast cancer. In this project we proposed to test whether combining an IDO inhibitor with paclitaxel could safely enhance efficacy against prostate tumors. The suggested model system was a variant of the TRAMP mouse engineered with a prostate-specific luciferase transgene. Briefly our objectives were to assign tumor-bearing mice to control and drug treatment groups and to compare tumor response after control or experimental therapies by bioluminescence imaging. Unfortunately a fatal pitfall prevented the use of the model nonselective luciferase expression. Two alternate models explored - each based on engraftment of luciferase-expressing cells into the prostate or under the skin - also exhibited fatal pitfalls arising tumors tended to spontaneously regress. Our findings raised serious concerns about the utility of luciferase-expressing prostate tumor cells for bioluminescence-based studies of prostate cancer pathophysiology and therapeutic response.
- Medicine and Medical Research