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Exploring Reovirus Plasticity for Improving Its Use as Oncolytic Virus
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Viruses 2016, 8(1), 9; doi:10.3390/v8010009

Overcoming Barriers in Oncolytic Virotherapy with HDAC Inhibitors and Immune Checkpoint Blockade

Infection, Inflammation and Cancer Program, Tumor Virology Division (F010), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
Current address: Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK
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Author to whom correspondence should be addressed.
Academic Editors: E. Antonio Chiocca and Martine L.M. Lamfers
Received: 30 September 2015 / Revised: 16 December 2015 / Accepted: 22 December 2015 / Published: 6 January 2016
(This article belongs to the Special Issue Oncolytic Viruses)
View Full-Text   |   Download PDF [10855 KB, uploaded 6 January 2016]   |  

Abstract

Oncolytic viruses (OVs) target and destroy cancer cells while sparing their normal counterparts. These viruses have been evaluated in numerous studies at both pre-clinical and clinical levels and the recent Food and Drug Administration (FDA) approval of an oncolytic herpesvirus-based treatment raises optimism that OVs will become a therapeutic option for cancer patients. However, to improve clinical outcome, there is a need to increase OV efficacy. In addition to killing cancer cells directly through lysis, OVs can stimulate the induction of anti-tumour immune responses. The host immune system thus represents a “double-edged sword” for oncolytic virotherapy: on the one hand, a robust anti-viral response will limit OV replication and spread; on the other hand, the immune-mediated component of OV therapy may be its most important anti-cancer mechanism. Although the relative contribution of direct viral oncolysis and indirect, immune-mediated oncosuppression to overall OV efficacy is unclear, it is likely that an initial period of vigorous OV multiplication and lytic activity will most optimally set the stage for subsequent adaptive anti-tumour immunity. In this review, we consider the use of histone deacetylase (HDAC) inhibitors as a means of boosting virus replication and lessening the negative impact of innate immunity on the direct oncolytic effect. We also discuss an alternative approach, aimed at potentiating OV-elicited anti-tumour immunity through the blockade of immune checkpoints. We conclude by proposing a two-phase combinatorial strategy in which initial OV replication and spread is maximised through transient HDAC inhibition, with anti-tumour immune responses subsequently enhanced by immune checkpoint blockade. View Full-Text
Keywords: oncolytic virus; cancer; combination therapy; HDAC inhibitors; immunotherapy; checkpoint immune blockade antibodies oncolytic virus; cancer; combination therapy; HDAC inhibitors; immunotherapy; checkpoint immune blockade antibodies
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Marchini, A.; Scott, E.M.; Rommelaere, J. Overcoming Barriers in Oncolytic Virotherapy with HDAC Inhibitors and Immune Checkpoint Blockade. Viruses 2016, 8, 9.

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