ADENOVIRUS-MEDIATED GENE-THERAPY OF OVARIAN-CANCER IN A MOUSE MODEL

OBJECTIVE: Our purpose was to test the feasibility of adenovirus-media ted gene therapy of ovarian cancer. STUDY DESIGN: Ovarian cancer cell lines were exposed to an adenovirus vector expressing a reporter gene (lacZ) and to the same vector bearing the herpes simplex virus thymidi ne kinase gene (Ad.RSVtk) followed by ganciclovir, lacZ expression and growth inhibition were quantitated. Immunodeficient mice were injecte d intraperitoneally and subcutaneously with human ovarian cancer cells and treated with Ad.RSVtk and ganciclovir. Statistical analyses inclu ded one-way analysis of variance and t tests. RESULTS: Staining for la cZ demonstrated viral transduction in vitro. After exposure to Ad.RSVt k all cell lines showed significant (p < 0.0001, analysis of variance) cytotoxicity to ganciclovir. Human ovarian tumor cells established su bcutaneously or intraperitoneally in immunodeficient mice responded to therapy with Ad.RSVtk followed by ganciclovir. Treated mice had a 10- to 20-fold lower subcutaneous tumor burden than did control mice. Add itionally, no intraperitoneal tumors were observed in treated mice. CO NCLUSIONS: Ovarian cancer cells are readily transduced with recombinan t adenovirus and become sensitive to ganciclovir after transduction wi th Ad.RSVtk. These data support the development of this method for hum an clinical trials.