A cyclooxygenase-2 promoter-based conditionally replicating adenovirus with enhanced infectivity for treatment of ovarian adenocarcinoma

A. Kanerva, G. J. Bauerschmitz, M. Yamamoto, J. T. Lam, R. D. Alvarez, G. P. Siegal, D. T. Curiel, Akseli Hemminki

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Conditionally replicating adenoviruses (CRADs) take advantage of tumor-specific characteristics for preferential replication and subsequent oncolysis of cancer cells. The antitumor effect is determined by the capability to infect tumor cells. Here, we used RGDCRADcox-2R, which features the cyclooxygenase-2 promoter for replication control and an integrin binding RGD-4C motif for enhanced infectivity of ovarian cancer cells. RGDCRADcox-2R replicated in and killed human ovarian cancer cells effectively, while the replication in nonmalignant cells was low. Importantly, the therapeutic efficacy, as evaluated in an orthotopic model of peritoneally disseminated ovarian cancer, was significantly improved and toxicity was lower than with a wild-type virus. Thus, this CRAD could be tested for treatment of ovarian cancer in humans.

Original languageEnglish
Pages (from-to)552-559
Number of pages8
JournalGene therapy
Volume11
Issue number6
DOIs
StatePublished - Mar 2004

Keywords

  • Adenovirus
  • Biological therapy
  • Ovarian neoplasms
  • Virus replication

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