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

Oncoimmunology
Rūta VeinaldeChristine E Engeland

Abstract

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.

References

Oct 1, 1993·The Journal of Experimental Medicine·M J BrundaM K Gately
Aug 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M J SmythS E Street
Mar 20, 2002·Cytokine & Growth Factor Reviews·Mario P Colombo, Giorgio Trinchieri
Mar 27, 2002·Nature Reviews. Immunology·Bernhard HomeyAlbert Zlotnik
Feb 4, 2003·Nature Reviews. Immunology·Giorgio Trinchieri
Mar 1, 1962·American Journal of Diseases of Children·A J SCHWARZ
Feb 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jun ChangYoung-Chul Sung
Feb 3, 2005·Nature Biotechnology·Takafumi NakamuraStephen J Russell
Aug 23, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Guy UngerechtsRoberto Cattaneo
Feb 11, 2009·Current Topics in Microbiology and Immunology·S J Russell, K W Peng
Feb 19, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sergia BortolanzaRuben Hernandez-Alcoceba
Apr 7, 2009·Methods in Molecular Biology·Derk AmsenTerrence Town
Dec 15, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·José Medina-EcheverzPedro Berraondo
Dec 16, 2011·Gene Therapy·O G DonnellyA A Melcher
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
Jan 23, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jean-Baptiste GuillermeMarc Gregoire
Jul 31, 2013·Immunity·Daniel S Chen, Ira Mellman
Aug 7, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Samuel T HaileSuzanne Ostrand-Rosenberg
Mar 19, 2014·Cell Host & Microbe·John Bell, Grant McFadden
Jul 6, 2014·Nature Reviews. Cancer·Brian D LichtyJohn C Bell
Aug 27, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christine E EngelandGuy Ungerechts
May 28, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Robert H I AndtbackaRobert S Coffin
Sep 2, 2015·Nature Reviews. Drug Discovery·Howard L KaufmanAndrew Zloza
Feb 26, 2016·Science Translational Medicine·Bernhard MlecnikJérôme Galon
Apr 9, 2016·Oncoimmunology·Jonathan PolLorenzo Galluzzi

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Citations

Aug 24, 2017·Viruses·Daniel N SantiagoHeiko Enderling
Dec 7, 2017·Oncoimmunology·Abhishek D GargLorenzo Galluzzi
Jun 7, 2018·Oncoimmunology·Elena García-MartínezLorenzo Galluzzi
Sep 6, 2017·Human Gene Therapy·Guy UngerechtsDirk M Nettelbeck
Sep 24, 2020·The EMBO Journal·Lingling WangTariq M Rana
Aug 5, 2019·World Journal of Pediatrics : WJP·Duo ZhouZheng-Yan Zhao
Dec 14, 2018·Oncoimmunology·Jonathan G PolLorenzo Galluzzi
Feb 27, 2020·Viruses·Elena BuschChristine E Engeland
May 15, 2018·Journal of the National Cancer Institute·Peter A Forsyth, Daniel Abate-Daga
Feb 14, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tobias SpeckChristine E Engeland
Feb 5, 2021·Cancers·Christine E Engeland, Guy Ungerechts
Nov 13, 2020·Frontiers in Immunology·Khue G NguyenDavid A Zaharoff
May 13, 2021·Nature Communications·D G RoyM-C Bourgeois-Daigneault
Jun 19, 2021·Molecular Therapy Oncolytics·Hans Martin SinghGuy Ungerechts
Nov 5, 2020·Molecular Therapy Oncolytics·Ianko D IankovEvanthia Galanis
Aug 28, 2021·International Journal of Molecular Sciences·Cole W D Peters, Fares Nigim

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Methods Mentioned

BETA
ELISA
flow cytometry
PCR
PCRs
FCS
electrophoresis
flow

Clinical Trials Mentioned

NCT00450814
NCT02364713
NCT01846091
NCT00390299
NCT01440816
NCT01502293
NCT01397708

Software Mentioned

GraphPad
GraphPad Prism
MeV
Normfinder
MeVac
FACS Diva

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