Expression of DAI by an oncolytic vaccinia virus boosts the immunogenicity of the virus and enhances antitumor immunity

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dc.contributor University of Helsinki, Faculty of Pharmacy en
dc.contributor University of Helsinki, Faculty of Pharmacy en
dc.contributor University of Helsinki, Research Programs Unit en
dc.contributor University of Helsinki, Faculty of Pharmacy en
dc.contributor University of Helsinki, Akseli Eetu Hemminki / Principal Investigator en
dc.contributor University of Helsinki, Faculty of Pharmacy en
dc.contributor University of Helsinki, Institute of Biotechnology en
dc.contributor University of Helsinki, Clinicum en
dc.contributor University of Helsinki, Faculty of Pharmacy en
dc.contributor.author Hirvinen, Mari
dc.contributor.author Capasso, Cristian
dc.contributor.author Guse, Kilian
dc.contributor.author Garofalo, Mariangela
dc.contributor.author Vitale, Andrea
dc.contributor.author Ahonen, Marko
dc.contributor.author Kuryk, Lukasz
dc.contributor.author Vähä-Koskela, Markus
dc.contributor.author Hemminki, Akseli
dc.contributor.author Fortino, Vittorio
dc.contributor.author Greco, Dario
dc.contributor.author Cerullo, Vincenzo
dc.date.accessioned 2017-09-12T11:23:01Z
dc.date.available 2017-09-12T11:23:01Z
dc.date.issued 2016-03-23
dc.identifier.citation Hirvinen , M , Capasso , C , Guse , K , Garofalo , M , Vitale , A , Ahonen , M , Kuryk , L , Vähä-Koskela , M , Hemminki , A , Fortino , V , Greco , D & Cerullo , V 2016 , ' Expression of DAI by an oncolytic vaccinia virus boosts the immunogenicity of the virus and enhances antitumor immunity ' , Molecular Therapy - Oncolytics , vol. 3 , 16002 . https://doi.org/10.1038/mto.2016.2 en
dc.identifier.issn 2372-7705
dc.identifier.other PURE: 77818818
dc.identifier.other PURE UUID: 360720c8-17f6-444d-a1f4-df223d7dbe3d
dc.identifier.other WOS: 000389446600001
dc.identifier.other Scopus: 84969253577
dc.identifier.uri http://hdl.handle.net/10138/222919
dc.description.abstract In oncolytic virotherapy, the ability of the virus to activate the immune system is a key attribute with regard to long-term antitumor effects. Vaccinia viruses bear one of the strongest oncolytic activities among all oncolytic viruses. However, its capacity for stimulation of antitumor immunity is not optimal, mainly due to its immunosuppressive nature. To overcome this problem, we developed an oncolytic VV that expresses intracellular pattern recognition receptor DNA-dependent activator of IFN-regulatory factors (DAI) to boost the innate immune system and to activate adaptive immune cells in the tumor. We showed that infection with DAI-expressing VV increases expression of several genes related to important immunological pathways. Treatment with DAI-armed VV resulted in significant reduction in the size of syngeneic melanoma tumors in mice. When the mice were rechallenged with the same tumor, DAI-VV-treated mice completely rejected growth of the new tumor, which indicates immunity established against the tumor. We also showed enhanced control of growth of human melanoma tumors and elevated levels of human T-cells in DAI-VV-treated mice humanized with human peripheral blood mononuclear cells. We conclude that expression of DAI by an oncolytic VV is a promising way to amplify the vaccine potency of an oncolytic vaccinia virus to trigger the innate-and eventually the long-lasting adaptive immunity against cancer. en
dc.format.extent 9
dc.language.iso eng
dc.relation.ispartof Molecular Therapy - Oncolytics
dc.rights en
dc.subject CANCER-THERAPY en
dc.subject POXVIRUS en
dc.subject VIRULENCE en
dc.subject LIGAND en
dc.subject 3122 Cancers en
dc.subject 3111 Biomedicine en
dc.subject 317 Pharmacy en
dc.title Expression of DAI by an oncolytic vaccinia virus boosts the immunogenicity of the virus and enhances antitumor immunity en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1038/mto.2016.2
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion
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