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The role of cyclophosphamide in enhancing antitumor efficacy of an adenovirus oncolytic vector in subcutaneous Syrian hamster tumors

Cancer Gene Therapy volume 20, pages 521–530 (2013)Cite this article

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Abstract

We have previously reported that intratumoral injection of VRX-007—an Ad5 (a species C adenovirus)-based vector overexpressing adenovirus death protein—can suppress the growth of subcutaneous HaK (hamster renal cancer) tumors. VRX-007 replication and tumor growth inhibition are enhanced when the hamsters are immunosuppressed by a high dose of cyclophosphamide (CP), an immunosuppressive and chemotherapeutic agent. Here, we report that continuous immunosuppression with CP was not required for increased oncolytic activity of VRX-007 because short-term dosing or continuous dosing with the drug yielded similar antitumor results. Prolonged viral replication was found only in animals on continuous CP treatment. We used 007-Luc, a replication-competent, luciferase-expressing vector similar to VRX-007, to investigate the replication of the vector over time. Tumor growth inhibition was similar in hamsters given CP treatment either 1 week before or 1 week after 007-Luc injection, which suggests that CP exerts its antitumor efficacy independently of vector therapy. 007-Luc did not spread far from the inoculation site, even in immunosuppressed, CP-treated animals. Our results indicate that the enhanced effectiveness that is produced by the combination of VRX-007 and CP therapies is due to their two independent mechanisms and that they do not have to be given simultaneously for the improved outcome.

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Acknowledgements

This study was supported by grant CA118022 from the National Institutes of Health. The VRX-007 vector was provided by VirRx, and WSMW, KT and AET own stocks in the company.

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Authors and Affiliations

  1. Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St Louis, MO, USA

    B A Young, J F Spencer, B Ying, A E Tollefson, K Toth & W S M Wold

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  1. B A Young
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Correspondence to K Toth.

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Supplementary Information accompanies the paper on the Cancer Gene Therapy website .

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Young, B., Spencer, J., Ying, B. et al. The role of cyclophosphamide in enhancing antitumor efficacy of an adenovirus oncolytic vector in subcutaneous Syrian hamster tumors. Cancer Gene Ther 20, 521–530 (2013). https://doi.org/10.1038/cgt.2013.49

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