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
Abstract
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 treatment strategies are needed. The subject of this work is a study of gene therapy, used alone and in combination with hormones called cytokines that stimulate the immune system. These genes will be delivered using lentivirus vectors. 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 (CDUPRT)) 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 producing CDUPRT convert 5-FC to a toxin that kills the original cell and others nearby. This system works in slow growing tumors like prostate cancer. Killing the tumor cells attracts immune cells. The scope of the work involves preparation of the gene vectors, optimizing the conditions required for delivering the genes of interest using lentivims vectors, and identification of the immune cells that infiltrate the tumor when gene therapy is used. We will identity these cells and use cytokine genes delivered into the tumor to attract more of them into tumors. We will then compare the effects of delivering the cytokine gene therapy alone, the suicide gene therapy alone, or a combination of both into mice that carry a murine prostate cancer cell line, RM1 cells, grown in the prostate.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2004
- Accession Number
- ADA423384
Entities
People
- Pamela J. Russell
Organizations
- University of New South Wales