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. New treatments are needed for late stage disease that has become refractory to hormone removal. 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 organ, coupled with help from the immune system can promote 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 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 others nearby. This system works in slow growing 5 like prostate cancer. Killing the cells attracts immune cells. We are using the cytokines, Interleukin- 12 or Interleukin- 18 either alone or in combination, to upregulate the immune response against the cancer. We will deliver the cytokine gene alone or with the suicide gene because in other studies, combination therapy works better.