Formulated Delivery of Enzyme/Pro-Drug and Cytokine Gene Therapy to Promote Immune Reduction of Treated and Remote Tumors in Mouse Models of Prostate Cancer

摘要

Prostate cancer is the second highest cause of cancer death in men in Western society. Early disease is treatable by surgery or radiation, but once late stage disease becomes refractory to hormone removal, patient care is limited to pain management. New treatments are needed, We use 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 deaminase and uracil phosphoribosyltransferase (CD/UPRT) is delivered to a cancer cell by a lentivirus so that harmless bacterial proteins are made. When followed by a pro-drug, 5 fluorocytosine (5FC), cancer cells that make CD/UPRT convert 5FC to a toxin that kills the original and neighboring cells. This system works in slow growing tumors like prostate cancer. Killing the tumor cells attracts immune cells. We are identifying these and then delivering cytokine genes that attract more immune cells into the tumors. We will deliver the cytokine gene alone or with the suicide gene because in other studies, combination therapy works better.