Ovarian cancer gene therapy using HPV-16 pseudovirion carrying the HSV-tk gene

• Published in: PloS one 2012-07, Vol.7 (7), p.e40983-e40983
• Main Authors: Hung, Chien-Fu, Chiang, An Jen, Tsai, Hsiao-Hsuan, Pomper, Martin G, Kang, Tae Heung, Roden, Richard R, Wu, T-C
• Format: Article
• Language: English
• Subjects: Animals; Anticancer properties; Antiviral Agents - pharmacology; Biology; Cancer; Cell Line; Cell Line, Tumor; Chemotherapy; Cytotoxicity; Deoxyribonucleic acid; Disease control; DNA; E coli; Enzymes; Escherichia coli; Female; Ganciclovir; Ganciclovir - pharmacology; Gene therapy; Genes; Genetic aspects; Genetic Therapy - methods; Genetic vectors; Gynecology; Health aspects; Herpes simplex; Human papillomavirus; Human papillomavirus 16 - genetics; Humans; Immunoglobulins; Infections; Injections, Intraperitoneal; Kinases; Medical innovations; Medicine; Mice; Mice, Inbred C57BL; Mice, Nude; Models, Genetic; Obstetrics; Oncology; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - genetics; Ovarian Neoplasms - therapy; Papillomavirus infections; Pathology; Proteins; Radiation therapy; Saccharomyces cerevisiae; Simplexvirus - metabolism; Suicides & suicide attempts; Surgery; Thymidine; Thymidine kinase; Thymidine Kinase - metabolism; TK gene; Tumor cells; Tumors; Vectors (Biology); Viruses; Yeast
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0040983

Ovarian cancer is the leading cause of death from all gynecological cancers and conventional therapies such as surgery, chemotherapy, and radiotherapy usually fail to control advanced stages of the disease. Thus, there is an urgent need for alternative and innovative therapeutic options. We reason that cancer gene therapy using a vector capable of specifically delivering an enzyme-encoding gene to ovarian cancer cells will allow the cancer cell to metabolize a harmless prodrug into a potent cytotoxin, which will lead to therapeutic effects. In the current study, we explore the use of a human papillomavirus (HPV) pseudovirion to deliver a herpes simplex virus thymidine kinase (HSV-tk) gene to ovarian tumor cells. We found that the HPV-16 pseudovirion was able to preferentially infect murine and human ovarian tumor cells when administered intraperitoneally. Furthermore, intraperitoneal injection of HPV-16 pseudovirions carrying the HSV-tk gene followed by treatment with ganciclovir led to significant therapeutic anti-tumor effects in murine ovarian cancer-bearing mice. Our data suggest that HPV pseudovirion may serve as a potential delivery vehicle for ovarian cancer gene therapy.