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

Gene Therapy volume 11, pages 552–559 (2004)Cite this article

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.

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Acknowledgements

We thank Drs Bin Liu and Minghui Wang (Division of Human Gene Therapy, University of Alabama at Birmingham) for statistical analysis and quantitative PCR assays. This work was supported by University of Helsinki Internal Funds, the Sigrid Juselius Foundation, Finnish Cancer Society, Biocentrum Helsinki, Emil Aaltonen Foundation, Maud Kuistila Foundation, Finnish Medical Foundation, Academy of Finland, Ida Montin Foundation, Biomedicum Helsinki-Foundation, the NIH (R01 CA94084, R01 CA83821, R01 CA93796, P50 CA83591), Susan B. Komen Foundation, Deutsche Forschungsgemeinschaft (BA2076/1-2), and University of Alabama Health Services Foundation. We thank Drs H Inoue and T Tanabe for providing a plasmid phPES3 containing the cox-2 promoter.

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Authors and Affiliations

  1. Rational Drug Design, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland

    A Kanerva & A Hemminki

  2. Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland

    A Kanerva & A Hemminki

  3. Division of Human Gene Therapy, Departments of Medicine, Pathology and Surgery, University of Alabama at Birmingham, Birmingham, AL, USA

    A Kanerva, GJ Bauerschmitz, M Yamamoto, JT Lam, DT Curiel & A Hemminki

  4. Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL, USA

    RD Alvarez

  5. Departments of Pathology, Cell Biology and Surgery, University of Alabama at Birmingham, Birmingham, AL, USA

    GP Siegal

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  1. A Kanerva
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Kanerva, A., Bauerschmitz, G., Yamamoto, M. et al. A cyclooxygenase-2 promoter-based conditionally replicating adenovirus with enhanced infectivity for treatment of ovarian adenocarcinoma. Gene Ther 11, 552–559 (2004). https://doi.org/10.1038/sj.gt.3302181

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