Oncolytic vesicular stomatitis virus expressing interferon-γ has enhanced therapeutic activity

dc.contributor.authorBourgeois-Daigneault, Marie-Claude
dc.contributor.authorRoy, Dominic Guy
dc.contributor.authorFalls, Theresa
dc.contributor.authorTwumasi-Boateng, Kwame
dc.contributor.authorSt-Germain, Lauren Elizabeth
dc.contributor.authorMarguerie, Monique
dc.contributor.authorGarcia, Vanessa
dc.contributor.authorSelman, Mohammed
dc.contributor.authorJennings, Victoria Ann
dc.contributor.authorPettigrew, Jessica
dc.contributor.authorAmos, Amos
dc.contributor.authorDiallo, Jean-Simon
dc.contributor.authorNelson, Brad
dc.contributor.authorBell, John Cameron
dc.date.accessioned2018-04-18T16:36:56Z
dc.date.available2018-04-18T16:36:56Z
dc.date.copyright2016en_US
dc.date.issued2016
dc.description.abstractOncolytic viruses are known to stimulate the antitumor immune response by specifically replicating in tumor cells. This is believed to be an important aspect of the durable responses observed in some patients and the field is rapidly moving toward immunotherapy. As a further means to engage the immune system, we engineered a virus, vesicular stomatitis virus (VSV), to encode the proinflammatory cytokine interferon-σ. We used the 4T1 mammary adenocarcinoma as well as other murine tumor models to characterize immune responses in tumor-bearing animals generated by treatment with our viruses. The interferon-σ-encoding virus demonstrated greater activation of dendritic cells and drove a more profound secretion of proinflammatory cytokines compared to the parental virus. From a therapeutic point of view, the interferon-σ virus slowed tumor growth, minimized lung tumors, and prolonged survival in several murine tumor models. The improved efficacy was lost in immunocompromized animals; hence the mechanism appears to be T-cell-mediated. Taken together, these results demonstrate the ability of oncolytic viruses to act as immune stimulators to drive antitumor immunity as well as their potential for targeted gene therapy.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipJ.C.B. is supported by the Terry Fox Foundation (TFF), the Canadian Cancer Society Research Institute (CCSRI), the Ontario Institute for Cancer Research (OICR), the Canadian Institute for Health Research (CIHR), the Ottawa Regional Cancer Foundation and the Ottawa Hospital Foundation. M-C.B-D., D.G.R., V.G., M.M., and M.S. were supported by fellowships and scholarships from the CIHR. K.T-B. was supported by a fellowship from Susan G. Komen. S.A. received a fellowship from the Canadian Breast Cancer Foundation (CBCF). J-S.D. was supported by the TFF, the CIHR and the CCSRI. Brad Nelson is supported by the Canadian Oncolytic Virus Consortium (COVCO), the CIHR, the TFF and the British Columbia Cancer Foundation.en_US
dc.identifier.citationBourgeois-Daigneault, M., Roy, D.R., Falls, T., Twumasi-Boateng, K., St-Germain, L.E., Marguerie, M., … Bell, J.C. (2016). Oncolytic vesicular stomatitis virus expressing interferon-γ has enhanced therapeutic activity. Molecular Therapy Oncolytics, 3, 16001. https://doi.org/10.1038/mto.2016.1en_US
dc.identifier.urihttps://doi.org/10.1038/mto.2016.1
dc.identifier.urihttp://hdl.handle.net/1828/9228
dc.language.isoenen_US
dc.publisherMolecular Therapy Oncolyticsen_US
dc.titleOncolytic vesicular stomatitis virus expressing interferon-γ has enhanced therapeutic activityen_US
dc.typeArticleen_US

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