title: In vivo gene therapy of ovarian cancer by adenovirus-mediated thymidine kinase gene transduction and ganciclovir administration.
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 microgram /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.
authors.affiliation: Departments of OB and Gyn, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: X W
authors.initials: XW
authors.lastname: Tong
authors.forename: A
authors.initials: A
authors.lastname: Block
authors.forename: S H
authors.initials: SH
authors.lastname: Chen
authors.forename: C F
authors.initials: CF
authors.lastname: Contant
authors.forename: I
authors.initials: I
authors.lastname: Agoulnik
authors.forename: K
authors.initials: K
authors.lastname: Blankenburg
authors.forename: R H
authors.initials: RH
authors.lastname: Kaufman
authors.forename: S L
authors.initials: SL
authors.lastname: Woo
authors.forename: D G
authors.initials: DG
authors.lastname: Kieback
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000628:therapy*; D016019:Survival Analysis; D013937:Thymidine Kinase / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D013937:Thymidine Kinase; D015774:Ganciclovir