Adenoviral-mediated p53 tumor suppressor gene therapy of human ovarian carcinoma

Kalpana Mujoo, Daniel C. Maneval, Scott C. Anderson, Jordan U. Gutterman

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

Mutations of p53 gene are reported in 50-60% of human cancers and reintroduction of wild-type p53 can suppress cell proliferation. In this study, replication deficient recombinant adenovirus encoding wild-type p53 (ACN53) under the control of the human cytomegalovirus (CMV) promoter was constructed. A specific incorporation of the p53 gene with ACN53 in SK-OV-3 (deleted p53 gene) cells was observed. ACN53 reduced the colony-forming ability of SK-OV-3 cells thereby supporting that 95-98% of cells are susceptible to infection by recombinant adenovirus. ACN53 inhibited the growth of 71-98% of SK-OV-3 cells 72-216 h after single infection. A highly aggressive ovarian xenograft model was established in which animals die between 25-45 days. A localization study with the adenovirus-containing β galactosidase reporter gene showed effective gene transfer in the tumor tissues. Ex vivo treatment of SK-OV-3 cells with ACN53 followed by injection into nude mice, increased the survival of the p53 treated mice by more than 50% compared with control animals. Gene therapy with ACN53 in intraperitoneal model of SK-OV-3 cells in two independent experiments revealed that there were some long-term survivors in the group of mice [2/5 (66 and 120 days) and [2/8 (166 and 423 days)) treated with ACN53. These findings demonstrate the potential of the p53 tumor suppressor gene therapy in human ovarian carcinoma.

Original languageEnglish (US)
Pages (from-to)1617-1623
Number of pages7
JournalOncogene
Volume12
Issue number8
StatePublished - 1996

Keywords

  • Adenoviral constructs
  • Gene therapy
  • Tumorigenicity
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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