OVARIAN CANCER SUICIDE GENE THERAPY WITH GENETICALLY ENGINEERED, TRANSGENICALLY EXPRESSED, INTRACELLULAR scFv ANTIBODIES AGAINST ANTI-OXIDATIVE ENZYMES.

Ovarian cancer is the leading cause of death among all gynecological cancers. Some women choose bilateral oophorectomy as means of cancer prevention. In most patients, by the time this cancer is diagnosed, it has already metastasized. Treatment involves oophorectomy followed by radiation, chemo-, and immuno-therapies. However, oopherectomy results in infertility and fails to eliminate all cancer cells. Radiation and chemotherapy cause severe side effects and may lead to genetic mutations in DNA of the ova.The ultimate goal of this project is development of a therapy which would target a therapeutic gene specific to ovarian cancer cells causing their apoptosis, but which would leave ova and other cells unharmed.Herein, we report the proof of concept for such a therapy, in which genetically engineered single chain variable fragment (scFv) antibodies against HER2/ neu, RON, and NK1R, guide the delivery of the therapeutic transgenes into the cancer cells of the ovaries. Under ovary specific promoters (OSP), the transgene expression generates the intracellular scFv antibodies, which quench cell antioxidative enzymes, thus raising levels of reactive oxygen species (ROS), inflicting oxidative stress, activating apoptotic signaling pathways, and causing cancer cell deaths.