Abstract
Interferons are circulating factors that bind to cell surface receptors, activating a signaling cascade, ultimately leading to both an antiviral response and an induction of growth inhibitory and/or apoptotic signals in normal and tumor cells1. Attempts to exploit the ability of interferons to limit the growth of tumors in patients has met with limited results2 because of cancer-specific mutations of gene products in the interferon pathway3,4,5,6,7. Although interferon-non-responsive cancer cells may have acquired a growth/survival advantage over their normal counterparts, they may have simultaneously compromised their antiviral response. To test this, we used vesicular stomatitis virus (VSV), an enveloped, negative-sense RNA virus8 exquisitely sensitive to treatment with interferon9. VSV rapidly replicated in and selectively killed a variety of human tumor cell lines even in the presence of doses of interferon that completely protected normal human primary cell cultures. A single intratumoral injection of VSV was effective in reducing the tumor burden of nude mice bearing subcutaneous human melanoma xenografts. Our results support the use of VSV as a replication-competent oncolytic virus and demonstrate a new strategy for the treatment of interferon non-responsive tumors.
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Acknowledgements
We thank D. Gray for aid in preparation and evaluation of the manuscript. This work was funded by a grant from the National Cancer Institute of Canada with funds from the Canadian Cancer Society and by the Ottawa Regional Cancer Centre Foundation. D.F.S was supported by an Ontario Graduate Scholarship in Science and Technology (OGSST).
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Stojdl, D., Lichty, B., Knowles, S. et al. Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat Med 6, 821–825 (2000). https://doi.org/10.1038/77558
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DOI: https://doi.org/10.1038/77558
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