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Gene Therapy Used in Cancer Treatment
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Tumor Restrictions to Oncolytic Virus

1
Institute of Biotechnology, University of Helsinki, Helsinki 00790, Finland
2
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio 70211, Finland
*
Authors to whom correspondence should be addressed.
Biomedicines 2014, 2(2), 163-194; https://doi.org/10.3390/biomedicines2020163
Received: 18 February 2014 / Revised: 17 March 2014 / Accepted: 28 March 2014 / Published: 17 April 2014
(This article belongs to the Special Issue Gene Therapy Used in Cancer Treatment)
Oncolytic virotherapy has advanced since the days of its conception but therapeutic efficacy in the clinics does not seem to reach the same level as in animal models. One reason is premature oncolytic virus clearance in humans, which is a reasonable assumption considering the immune-stimulating nature of the oncolytic agents. However, several studies are beginning to reveal layers of restriction to oncolytic virotherapy that are present before an adaptive neutralizing immune response. Some of these barriers are present constitutively halting infection before it even begins, whereas others are raised by minute cues triggered by virus infection. Indeed, we and others have noticed that delivering viruses to tumors may not be the biggest obstacle to successful therapy, but instead the physical make-up of the tumor and its capacity to mount antiviral defenses seem to be the most important efficacy determinants. In this review, we summarize the constitutive and innate barriers to oncolytic virotherapy and discuss strategies to overcome them. View Full-Text
Keywords: oncolytic virus; interferon; tumor stroma; antiviral defenses; extracellular matrix; tight junctions oncolytic virus; interferon; tumor stroma; antiviral defenses; extracellular matrix; tight junctions
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Vähä-Koskela, M.; Hinkkanen, A. Tumor Restrictions to Oncolytic Virus. Biomedicines 2014, 2, 163-194.

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