Adenoviral-mediated suicide gene therapy for ovarian cancer

Ronald D. Alvarez, Jesus Gomez-Navarro, Minghui Wang, Mack N. Barnes, Theresa V. Strong, Ramin B. Arani, Waleed Arafat, Joseph V. Hughes, Gene P. Siegal, David T. Curiel

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

The purpose of this phase I study was to determine the potential efficacy of adenoviral-mediated suicide gene therapy in women with recurrent ovarian cancer. Fourteen patients were treated intraperitoneally with herpes simplex virus-thymidine kinase (HSV-TK)-encoding adenovirus (AdHSV-TK) in dosages rang ing between 1 × 109 and 1 × 1011 pfu. Beginning 2 days later, ganciclovir (GCV) was administered intravenously at a dose of 5 mg/kg bid for 14 days. Transient vector-associated fever was experienced by 4 of 14 (29%) treated patients. Other possible vector-associated constitutional symptoms, abdominal pain, and gastrointestinal symptoms were experienced by 6 of 14 (43%) treated patients. No other dose-limiting vector-specific side effects were noted. Of the 13 patients evaluable for response, 5 (38%) had stable disease and 8 (62%) had evidence of progressive disease. Molecular analysis of évaluable ascites samples demonstrated the presence of transgene DNA and RNA in most patients 2 days following Ad HSV-TK administration. Ten of 11 evaluable patients had an increase in anti-adenovirus antibody titer. These results suggest that treatment with AdHSV-TK in combination with GCV is feasible in the context of human ovarian cancer and tolerated at the dosages studied.

Original languageEnglish
Pages (from-to)524-530
Number of pages7
JournalMolecular Therapy
Volume2
Issue number5
DOIs
StatePublished - Nov 2000

Keywords

  • Gene therapy
  • Ovarian cancer
  • Recombinant adenovirus
  • Suicide gene therapy

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