Adenoviral-mediated suicide gene therapy for ovarian cancer.

Academic Article

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 ranging between 1x10(9) and 1x10(11) 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 evaluable 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.
  • Published In

  • Molecular Therapy  Journal
  • Keywords

  • Adenoviridae, Adult, Aged, Antibodies, Viral, DNA, Viral, Drug Administration Schedule, Female, Ganciclovir, Gene Expression, Genetic Therapy, Genetic Vectors, Humans, Injections, Intraperitoneal, Middle Aged, Ovarian Neoplasms, Simplexvirus, Thymidine Kinase, Transgenes
  • Digital Object Identifier (doi)

    Author List

  • Alvarez RD; Gomez-Navarro J; Wang M; Barnes MN; Strong TV; Arani RB; Arafat W; Hughes JV; Siegal GP; Curiel DT
  • Start Page

  • 524
  • End Page

  • 530
  • Volume

  • 2
  • Issue

  • 5