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Oncolytic virotherapy for ovarian carcinomatosis using a replication-selective vaccinia virus armed with a yeast cytosine deaminase gene

Cancer Gene Therapy volume 15, pages 115–125 (2008)Cite this article

Abstract

In this study, we assessed the ability of a highly tumor-selective oncolytic vaccinia virus armed with a yeast cytosine deaminase gene to infect and lyse human and murine ovarian tumors both in vitro and in vivo. The virus vvDD-CD could infect, replicate in and effectively lyse both human and mouse ovarian cancer cells in vitro. In two different treatment schedules involving either murine MOSEC or human A2780 ovarian carcinomatosis models, regional delivery of vvDD-CD selectively targeted tumor cells and ovarian tissue, effectively delaying the development of either tumor or ascites and leading to significant survival advantages. Oncolytic virotherapy using vvDD-CD in combination with the prodrug 5-fluorocytosine conferred an additional long-term survival advantage upon tumor-bearing immunocompetent mice. These findings demonstrate that a tumor-selective oncolytic vaccinia combined with gene-directed enzyme prodrug therapy is a highly effective strategy for treating advanced ovarian cancers in both syngeneic mouse and human xenograft models. Given the biological safety, tumor selectivity and oncolytic potency of this armed oncolytic virus, this dual therapy merits further investigation as a promising new treatment for metastatic ovarian cancer.

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Acknowledgements

We thank Dr Ta-Chiang Liu, Dr David Kirn and Dr Bingliang Fang for critical reading of the manuscript, Dr Katherine Roby for MOSEC ovarian cancer cells and Dr Julie A DeLoia for primary human ovarian cancer cells. We also thank Ms Eve Blasko for excellent administrative assistance. This work was supported in part by the NIH R01 Grant CA100415, the Intramural Research Program of the NIH and by David C Koch Regional Cancer Therapy Center.

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Authors and Affiliations

  1. Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    S Chalikonda, M E O'Malley, X D (Eric) Dong, M C Gorry, X-Y Yin, C K Brown, H J Zeh III, Z S Guo & D L Bartlett

  2. Surgery Branch, National Cancer Institute, NIH, Bethesda, MD, USA

    M H Kivlen, J A McCart & D L Bartlett

  3. Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China

    X-Y Yin

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  1. S Chalikonda
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Correspondence to Z S Guo.

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Part of this work was presented at an oral session at the 9th Annual Meeting of the American Society of Gene Therapy in Baltimore, MD, June 2006.

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Chalikonda, S., Kivlen, M., O'Malley, M. et al. Oncolytic virotherapy for ovarian carcinomatosis using a replication-selective vaccinia virus armed with a yeast cytosine deaminase gene. Cancer Gene Ther 15, 115–125 (2008). https://doi.org/10.1038/sj.cgt.7701110

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