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The role of natural killer cells in combinatorial anti-cancer therapy using Sindbis viral vectors and irinotecan

Cancer Gene Therapy volume 19, pages 588–591 (2012)Cite this article

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Abstract

Oncolytic viruses (OVs) have shown great anti-cancer potential in animal models, but only modest success in early clinical trials. A better understanding of the mechanisms underlining OV efficacy is needed to resolve this discrepancy. In the clinic, OV therapy will likely be combined with traditional chemotherapy, underscoring the need to also evaluate the interactions between these therapeutic modalities. Here we show that combining Sindbis viral vector therapy with the topoisomerase inhibitor irinotecan (CPT-11) results in the long-term survival of about 35% of SCID mice bearing aggressively growing ES2 human ovarian cancer. Single-agent treatments did not result in long-term survival. Flow cytometry analysis, bioluminescent imaging and survival experiments revealed that Sindbis and CPT-11 utilize non-overlapping natural killer (NK)-cell-dependent and -independent anti-cancer mechanisms, respectively. Notably, the combinatorial therapy was only effective in the presence of NK cells. These results highlight the hidden role of immune cell activation in combinatorial cancer therapy involving OVs and provide a potential method for tackling tumor cell resistance to cancer therapy while limiting treatment-related side effects.

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Acknowledgements

We thank Dr Christine Pampeno and Vincent DiGiacomo for critical reading of this manuscript. This work was supported by the US Public Health grants CA100687 from the National Cancer Institute, National Institutes of Health and Department of Health and Human Services. Funding was also provided by a gift from the Litwin Foundation and a Research and License agreement between NYU and CynVec.

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  1. Department of Pathology, NYU Cancer Institute, NYU Gene Therapy Center, NYU School of Medicine, New York, NY, USA

    T Granot & D Meruelo

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  1. T Granot
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Correspondence to D Meruelo.

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The contents of this paper are being utilized for a patent. According to the rules and regulations of New York University School of Medicine, if this patent is licensed by a third party, the authors (DM, TG) may receive benefits in the form of royalties or equity participation.

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Granot, T., Meruelo, D. The role of natural killer cells in combinatorial anti-cancer therapy using Sindbis viral vectors and irinotecan. Cancer Gene Ther 19, 588–591 (2012). https://doi.org/10.1038/cgt.2012.33

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