Augmentation of a Novel Enzyme/Pro-Drug Gene Therapy 'Distant Bystander Effect' to Target Prostate Cancer Metastasis

摘要

Prostate cancer is now the second highest cause of cancer death in men in Western society. Early disease is treatable by surgery and radiation, but once late stage disease becomes refractory to hormone removal, patient care is limited to pain management. New treatments are needed. We are using gene therapy, alone and in combination with hormones called cytokines that stimulate the immune system. The concept is that delivering a cell-killing agent to an accessible tumor, coupled with help from the immune system can promote tumor reduction both at the treatment site and at remote locations. In this therapy, a gene (a fusion of cytosine dreaminase and uracil phosphoribosyltransferase (DC/ UPRT)) is delivered to a cancer cell so that harmless bacterial proteins are made. When a pro-drug, 5 fluorocytosine (5-FC), is then given, cancer cells that make CD/UPRT convert 5-FC to a toxin that kills the original cell and other nearby. This system works in slow growing tumors like prostate cancer. Killing the tumor cells attracts immune cells. We will identify these and use cytokinase to attract more of them into tumors. We will deliver the cytokine gene alone or with the suicide gene because in other studies, combination therapy works better.