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Viruses 2015, 7(11), 5889-5901; doi:10.3390/v7112914

Harnessing the Power of Onco-Immunotherapy with Checkpoint Inhibitors

1
Department of Molecular Medicine; Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
2
Department of Immunology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
*
Author to whom correspondence should be addressed.
Academic Editors: E. Antonio Chiocca and Martine L.M. Lamfers
Received: 31 August 2015 / Revised: 26 October 2015 / Accepted: 29 October 2015 / Published: 13 November 2015
(This article belongs to the Special Issue Oncolytic Viruses)
View Full-Text   |   Download PDF [208 KB, uploaded 13 November 2015]   |  

Abstract

Oncolytic viruses represent a diverse class of replication competent viruses that curtail tumor growth. These viruses, through their natural ability or through genetic modifications, can selectively replicate within tumor cells and induce cell death while leaving normal cells intact. Apart from the direct oncolytic activity, these viruses mediate tumor cell death via the induction of innate and adaptive immune responses. The field of oncolytic viruses has seen substantial advancement with the progression of numerous oncolytic viruses in various phases of clinical trials. Tumors employ a plethora of mechanisms to establish growth and subsequently metastasize. These include evasion of immune surveillance by inducing up-regulation of checkpoint proteins which function to abrogate T cell effector functions. Currently, antibodies blocking checkpoint proteins such as anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) have been approved to treat cancer and shown to impart durable clinical responses. These antibodies typically need pre-existing active immune tumor microenvironment to establish durable clinical outcomes and not every patient responds to these therapies. This review provides an overview of published pre-clinical studies demonstrating superior therapeutic efficacy of combining oncolytic viruses with checkpoint blockade compared to monotherapies. These studies provide compelling evidence that oncolytic therapy can be potentiated by coupling it with checkpoint therapies. View Full-Text
Keywords: oncolytic viruses; checkpoint inhibitors; anti-PD-1; anti-CTLA-4; immunotherapy; oncoimmunotherapy; innate and adaptive immunity; immune-evasion oncolytic viruses; checkpoint inhibitors; anti-PD-1; anti-CTLA-4; immunotherapy; oncoimmunotherapy; innate and adaptive immunity; immune-evasion
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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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MDPI and ACS Style

Rajani, K.R.; Vile, R.G. Harnessing the Power of Onco-Immunotherapy with Checkpoint Inhibitors. Viruses 2015, 7, 5889-5901.

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