Adenovirus-mediated gene therapy of ovarian cancer in a mouse model

Abstract

OBJECTIVE: Our purpose was to test the feasibility of adenovirus-mediated 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 thymidine kinase gene (Ad.RSV tk) followed by ganciclovir. lacZ expression and growth inhibition were quantitated. Immunodeficient mice were injected intraperitoneally and subcutaneously with human ovarian cancer cells and treated with Ad.RSV tk and ganciclovir. Statistical analyses included one-way analysis of variance and t tests. RESULTS: Staining for lacZ demonstrated viral transduction in vitro. After exposure to Ad.RSV tk all cell lines showed significant ( p < 0.0001, analysis of variance) cytotoxicity to ganciclovir. Human ovarian tumor cells established subcutaneously or intraperitoneally in immunodeficient mice responded to therapy with Ad.RSV tk followed by ganciclovir. Treated mice had a 10- to 20-fold lower subcutaneous tumor burden than did control mice. Additionally, no intraperitoneal tumors were observed in treated mice. CONCLUSIONS: Ovarian cancer cells are readily transduced with recombinant adenovirus and become sensitive to ganciclovir after transduction with Ad.RSV tk. These data support the development of this method for human clinical trials. (Am J Obstet Gynecol 1996;175:1260-5.)