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Synergistic antitumour effects of rapamycin and oncolytic reovirus

Cancer Gene Therapy volume 25, pages 148–160 (2018)Cite this article

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Abstract

There are currently numerous oncolytic viruses undergoing clinical trial evaluation in cancer patients and one agent, Talimogene laherparepvec, has been approved for the treatment of malignant melanoma. This progress highlights the huge clinical potential of this treatment modality, and the focus is now combining these agents with conventional anticancer treatments or agents that enhance viral replication, and thereby oncolysis, in the tumour microenvironment. We evaluated the combination of reovirus with rapamycin in B16F10 cell, a murine model of malignant melanoma, based on potential mechanisms by which mTOR inhibitors might enhance viral oncolysis. Rapamycin was not immunomodulatory in that it had no effect on the generation of an antireovirus-neutralising antibody response in C57/black 6 mice. The cell cycle effects of reovirus (increase G0/G1 fraction) were unaffected by concomitant or sequential exposure of rapamycin. However, rapamycin attenuated viral replication if given prior or concomitantly with reovirus and similarly reduced reovirus-induced apoptotic cell death Annexin V/PI and caspase 3/7 activation studies. We found clear evidence of synergistic antitumour effects of the combination both in vitro and in vivo, which was sequence dependent only in the in vitro setting. In conclusion, we have demonstrated synergistic antitumour efficacy of reovirus and rapamycin combination.

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Authors and Affiliations

  1. Oncology, Faculty of Health and Medical Sciences, University of Surrey, Leggett Building, Guildford, Surrey, GU2 7WG, UK

    Charles Comins, Guy Richard Simpson, William Rogers, Kate Relph & Hardev Pandha

  2. Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP, UK

    Kevin Harrington, Alan Melcher, Victoria Roulstone & Joan Kyula

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  1. Charles Comins
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Comins, C., Simpson, G.R., Rogers, W. et al. Synergistic antitumour effects of rapamycin and oncolytic reovirus. Cancer Gene Ther 25, 148–160 (2018). https://doi.org/10.1038/s41417-018-0011-8

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