Ovarian cancer gene therapy: Repeated treatment with thymidine kinase in an adenovirus vector and ganciclovir improves survival in a novel immunocompetent murine model

Ayman Al-Hendy, Anthony M. Magliocco, Taher Al-Tweigeri, George Braileanu, Natasha Crellin, Hui Li, Theresa Strong, David Curiel, P. Jorge Chedrese

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: Our purpose was to assess the effect of multiple injections of the system of herpes simplex virus thymidine kinase in an adenovirus vector and ganciclovir on survival in a murine model of human epithelial ovarian cancer. STUDY DESIGN: In this work we tested the ability of the system of thymidine kinase delivered by an adenovirus vector and ganciclovir to treat ovarian cancer in a novel murine model for epithelial ovarian cancer, SaskMouse. SaskMouse was developed by injecting LM-1 cells, a murine epithelial ovarian cancer cell line, intraperitoneally into a syngeneic C57BL/6N x C3H/He mouse strain. The cells developed into multiple cancer implants on different abdominal organs, leading to ascites and rapid death. The model has an intact immune system, as evidenced by the inability of different human cancer cells to develop into cancers when injected into the mice intraperitoneally. RESULTS: The system of thymidine kinase delivered by an adenovirus vector and ganciclovir was applied to SaskMouse. Mice were either untreated (group 1), treated with one intraperitoneal injection of adenovirus-thymidine kinase at 250 plaque-forming units/cell (group 2), or treated with two intraperitoneal injections of adenovirus-thymidine kinase at 250 plaque-forming units/cell on days 0 and 23 (group 3). Survivals were 23 ± 2, 27 ± 2, and 35 ± 4 days, respectively (P < .05). Antiadenoviral antibodies were assayed both in the serum and in the peritoneal fluid of treated mice. Despite high antibody titers in serum, there were no detectable antibodies in the peritoneal fluid. CONCLUSION: Our data suggest that multiple intraperitoneal injections of the combination of thymidine kinase delivered by an adenovirus vector and ganciclovir are effective in prolonging survival in the presence of ovarian cancer. There are potential implications for other abdominal malignancies.

Original languageEnglish (US)
Pages (from-to)553-559
Number of pages7
JournalAmerican Journal of Obstetrics and Gynecology
Volume182
Issue number3
DOIs
StatePublished - Jan 1 2000

Fingerprint

Ganciclovir
Thymidine Kinase
Neoplasm Genes
Adenoviridae
Genetic Therapy
Ovarian Neoplasms
Survival
Intraperitoneal Injections
Ascitic Fluid
Antibodies
Neoplasms
Therapeutics
Inbred C3H Mouse
Simplexvirus
Serum
Ascites
Immune System
Cell Line
Injections
Ovarian epithelial cancer

Keywords

  • Adenovirus
  • Antibodies
  • Gene therapy
  • Ovarian cancer

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Ovarian cancer gene therapy : Repeated treatment with thymidine kinase in an adenovirus vector and ganciclovir improves survival in a novel immunocompetent murine model. / Al-Hendy, Ayman; Magliocco, Anthony M.; Al-Tweigeri, Taher; Braileanu, George; Crellin, Natasha; Li, Hui; Strong, Theresa; Curiel, David; Chedrese, P. Jorge.

In: American Journal of Obstetrics and Gynecology, Vol. 182, No. 3, 01.01.2000, p. 553-559.

Research output: Contribution to journalArticle

Al-Hendy, Ayman ; Magliocco, Anthony M. ; Al-Tweigeri, Taher ; Braileanu, George ; Crellin, Natasha ; Li, Hui ; Strong, Theresa ; Curiel, David ; Chedrese, P. Jorge. / Ovarian cancer gene therapy : Repeated treatment with thymidine kinase in an adenovirus vector and ganciclovir improves survival in a novel immunocompetent murine model. In: American Journal of Obstetrics and Gynecology. 2000 ; Vol. 182, No. 3. pp. 553-559.
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AU - Al-Tweigeri, Taher

AU - Braileanu, George

AU - Crellin, Natasha

AU - Li, Hui

AU - Strong, Theresa

AU - Curiel, David

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