In Vivo Gene Therapy of Ovarian Cancer by Adenovirus-Mediated Thymidine Kinase Gene Transduction and Ganciclovir Administration

Author： Tong X.-.W. Block A. Chen S.-.H. Contant C.F. Agoulnik I. Blankenburg K. Kaufman R.H. Woo S.L.C. Kieback D.G.

Publisher： Academic Press

ISSN： 0090-8258

Source： Gynecologic Oncology, Vol.61, Iss.2, 1996-05, pp. : 175-179

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

Efficacy and toxicity of adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene followed by administration of ganciclovir were studied in vivo. A human epithelial ovarian cancer animal model was established in nude mice using the serous ovarian adenocarcinoma cell line Ov-ca-2774. Intraperitoneal (ip) injection of 1 x 10 8 Ov-ca-2774 cells resulted in tumor growth and formation of malignant ascites in all 15 animals. In a prospective randomized experimental design mice were treated 1, 3, or 7 days after ip injection of 1 x 10 8 cells with ip injection of 2 x 10 8 , 6.7 x 10 8 , or 2 x 10 9 pfu ADV.RSV-TK followed by administration of ganciclovir (10 mug/ml, ip, bid) for 6 consecutive days. End points were survival and toxicity. Mice treated with GCV or HSV-TK alone died from 14.4 ± 1.7 to 19.5 ± 3.5 days after treatment as did untreated controls. No toxicity of ADV.RSV-TK was found up to 2 x 10 9 pfu (2 x 10 11 particles). The mice with the highest tumor burden treated with the lowest viral dose lived significantly longer than controls ( P < 0.05). Median survival in all other groups of mice treated with ADV.RSV-TK plus GCV was even longer ( P < 0.01). Treatment benefit was dependent on ADV/RSV-TK dose and tumor burden. Adenovirus-mediated thymidine kinase gene therapy is a realistic approach to ovarian cancer treatment that warrants investigation in the clinical setting.