Immunogenic HSV-mediated oncolysis shapes the antitumor immune response and contributes to therapeutic efficacy

Molecular Therapy : the Journal of the American Society of Gene Therapy
Samuel T WorkenheKaren L Mossman

Abstract

Within the oncolytic virus field, the extent of virus replication that is essential for immune stimulation to control tumor growth remains unresolved. Using infected cell protein 0 (ICP0)-defective oncolytic Herpes simplex virus type 1 (HSV-1) and HSV-2 viruses (dICP0 and dNLS) that show differences in their in vitro replication and cytotoxicity, we investigated the inherent features of oncolytic HSV viruses that are required for potent antitumor activity. In vitro, the HSV-2 vectors showed rapid cytotoxicity despite lower viral burst sizes compared to HSV-1 vectors. In vivo, although both of the dICP0 vectors initially replicated to a similar level, HSV-1 dICP0 was rapidly cleared from the tumors. In spite of this rapid clearance, HSV-1 dICP0 treatment conferred significant survival benefit. HSV-1 dICP0-treated tumors showed significantly higher levels of danger-associated molecular patterns that correlated with higher numbers of antigen-presenting cells within the tumor and increased antigen-specific CD8+ T-cell levels in the peripheral blood. This study suggests that, at least in the context of oncolytic HSV, the initial stages of immunogenic virus replication leading to activation of antitumor immunity are more important th...Continue Reading

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Citations

Feb 17, 2015·Future Oncology·Samuel T WorkenheKaren L Mossman
Apr 8, 2015·Current Opinion in Virology·Breanne P Cuddington, Karen L Mossman
Oct 16, 2015·Molecular Therapy Oncolytics·Cole Peters, Samuel D Rabkin
Aug 7, 2014·Oncoimmunology·Jonathan PolLorenzo Galluzzi
Aug 8, 2014·Frontiers in Oncology·Norman WollerFlorian Kühnel
May 2, 2014·Frontiers in Oncology·Zong Sheng GuoDavid L Bartlett
Jul 6, 2014·Frontiers in Oncology·Steve H Thorne
Aug 1, 2018·Viruses·Amy L MacNeillBarbara E Powers
Jul 3, 2019·Journal for Immunotherapy of Cancer·Louise M E MüllerFiona Errington-Mais
May 31, 2017·Frontiers in Immunology·Zong Sheng GuoDavid L Bartlett
May 26, 2017·Biomedicines·Amelia Sadie AitkenMarie-Claude Bourgeois-Daigneault
Jul 20, 2017·Journal of Leukocyte Biology·Jolien De MunckJoeri L Aerts
Aug 21, 2020·Applied Microbiology and Biotechnology·Pei-Yang HuXiao-Zhou Mou
Jun 1, 2017·Frontiers in Pharmacology·Dhaval S SanchalaKedar S Prabhavalkar
Apr 27, 2018·Nature Reviews. Cancer·Kwame Twumasi-BoatengBrad H Nelson
Feb 14, 2019·Scientific Reports·Nikolas Tim MartinMarie-Claude Bourgeois-Daigneault
Nov 13, 2018·Future Virology·Leslee SpragueTimothy P Cripe
May 10, 2019·Oncoimmunology·Maria Eugenia Davola, Karen Louise Mossman
Mar 16, 2021·Oncoimmunology·Samuel T WorkenheGuido Kroemer
May 20, 2021·Bulletin of Mathematical Biology·Noma Susan SenekalRachid Ouifki
Jun 19, 2021·Frontiers in Oncology·Thijs A van SchaikKhalid Shah
Aug 11, 2021·Viruses·Chase KangasBin He
Aug 29, 2021·Viruses·Laura HofmanMartine L M Lamfers
May 28, 2019·Advanced Drug Delivery Reviews·Yoosoo YangIn-San Kim

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