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Oncolytic measles virus encoding interleukin-12 mediates potent antitumor effects through T cell activation

Combination of oncolytic virotherapy with immunomodulators is emerging as a promising therapeutic strategy for numerous tumor entities. In this study, we developed measles Schwarz vaccine strain vectors encoding immunomodulators to support different phases in the establishment of antitumor immune re...

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Bibliographic Details
Main Authors: Veinalde, Rūta (Author) , Großardt, Christian (Author) , Hartmann, Laura (Author) , Jäger, Dirk (Author) , Kalle, Christof von (Author) , Ungerechts, Guy (Author) , Engeland, Christine Elisabeth (Author)
Format: Article (Journal)
Language:English
Published: 2017 Jan 31
In: OncoImmunology
Year: 2017, Volume: 6, Issue: 4
ISSN:2162-402X
DOI:10.1080/2162402X.2017.1285992
Online Access:Verlag, Volltext: http://dx.doi.org/10.1080/2162402X.2017.1285992
Verlag, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414860/
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Author Notes:Rūta Veinalde, Christian Grossardt, Laura Hartmann, Marie-Claude Bourgeois-Daigneault, John C. Bell, Dirk Jäger, Christof von Kalle, Guy Ungerechts, and Christine E. Engeland
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Summary:Combination of oncolytic virotherapy with immunomodulators is emerging as a promising therapeutic strategy for numerous tumor entities. In this study, we developed measles Schwarz vaccine strain vectors encoding immunomodulators to support different phases in the establishment of antitumor immune responses. Therapeutic efficacy of the novel vectors was evaluated in the immunocompetent MC38cea tumor model. We identified vectors encoding an IL-12 fusion protein (MeVac FmIL-12) and an antibody against PD-L1 (MeVac anti-PD-L1), respectively, as the most effective. Treatment of established tumors with MeVac FmIL-12 achieved 90% complete remissions. Profiling of the tumor immune microenvironment revealed activation of a type 1 T helper cell-directed response, with MeVac FmIL-12 ensuring potent early natural killer and effector T cell activation as well as upregulation of the effector cytokines IFN-γ and TNF-α. CD8+ T cells were found to be essential for the therapeutic efficacy of MeVac FmIL-12. Results of this study present MeVac FmIL-12 as a novel approach for targeted IL-12 delivery and elucidate mechanisms of successful immunovirotherapy.
Item Description:Gesehen am 05.09.2018
Physical Description:Online Resource
ISSN:2162-402X
DOI:10.1080/2162402X.2017.1285992

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