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

American Journal of Obstetrics and Gynecology
K BehbakhtJ Boyd

Abstract

Our purpose was to test the feasibility of adenovirus-mediated gene therapy of ovarian cancer. 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.RSVtk) 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.RSVtk and ganciclovir. Statistical analyses included one-way analysis of variance and t tests. Staining for lacZ demonstrated viral transduction in vitro. After exposure to Ad.RSVtk 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.RSVtk 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. Ovarian cancer cells are readily transduced with recombinant adenovirus and become sensitive to ganciclovir after transduction with Ad.RSVtk. These data support th...Continue Reading

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Citations

Feb 27, 1999·Human Gene Therapy·M Y HurwitzR L Hurwitz
Dec 1, 2001·Expert Opinion on Biological Therapy·J B Alavi, S L Eck
Sep 10, 2003·Hematology/oncology Clinics of North America·Tyler O KirbyRonald D Alvarez
Nov 18, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·R D AlvarezD T Curiel
Nov 26, 2008·Acta Pharmacologica Sinica·Wen-fang Shi, Jeffrey S Bartlett
Sep 22, 1999·Gene Therapy·M LanutiS Albelda
Jul 24, 1998·Biochemical and Biophysical Research Communications·K Sawai, D Meruelo

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