EPISOMAL VECTORS FOR BREAST CANCER GENE THERAPY

Copernicus Therapeutics, Inc., Cleveland OH

Investigators

Abstract

Gene therapy is currently being used to treat a variety of cancers, including brain, prostate and ovarian carcinoma. However, there are many obstacles that need to be overcome if gene transfer technologies are to be fully exploited. A significant obstacle in the development of non- viral vectors is the rapid decline of gene expression in transiently transfected tumor cells. To overcome this deficiency, Copernicus has developed a novel SV40 large T antigen mutant to drive extrachromosomal replication of plasmids containing an SV40 DNA origin. This safety-modified T antigen is unable to bind host tumor suppressor gene products but remains replication-competent, allowing the vector to replicate to several thousand copies per human cell, and yielding high levels of gene expression. By fusing a portion of the hormone binding domain of the human progesterone receptor, we able to externally-control vector amplification using the FDA-approved progesterone antagonist RU486. We now propose to develop a breast cancer specific episomal expression system utilizing our safety-modified, externally-regulated episomal expression vector. PROPOSED COMMERCIAL APPLICATIONS: Non-viral gene therapy expression vectors are limited by modest levels of gene expression. We have developed an episomal plasmid vector that replicates extrachromosomally in human cells under external control, and generates high levels of gene expression. This episomal vector has the potential to be an effective cancer therapeutic, and could be incorporated into treatments for diverse cancer indications.