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

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http://hdl.handle.net/10138/222919

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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

Titel: Expression of DAI by an oncolytic vaccinia virus boosts the immunogenicity of the virus and enhances antitumor immunity
Författare: Hirvinen, Mari; Capasso, Cristian; Guse, Kilian; Garofalo, Mariangela; Vitale, Andrea; Ahonen, Marko; Kuryk, Lukasz; Vähä-Koskela, Markus; Hemminki, Akseli; Fortino, Vittorio; Greco, Dario; Cerullo, Vincenzo
Medarbetare: University of Helsinki, Faculty of Pharmacy
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Research Programs Unit
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Akseli Eetu Hemminki / Principal Investigator
University of Helsinki, Faculty of Pharmacy
University of Helsinki, Institute of Biotechnology
University of Helsinki, Clinicum
University of Helsinki, Faculty of Pharmacy
Datum: 2016-03-23
Språk: eng
Sidantal: 9
Tillhör serie: Molecular Therapy - Oncolytics
ISSN: 2372-7705
Permanenta länken (URI): http://hdl.handle.net/10138/222919
Abstrakt: 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.
Subject: CANCER-THERAPY
POXVIRUS
VIRULENCE
LIGAND
3122 Cancers
3111 Biomedicine
317 Pharmacy
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