Samson, A orcid.org/0000-0002-3081-7850, Bentham, MJ orcid.org/0000-0003-2439-3198, Scott, K orcid.org/0000-0002-5790-9579 et al. (15 more authors) (2018) Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer. Gut, 67 (3). pp. 562-573. ISSN 0017-5749
Abstract
Objective: Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer. Design and results: Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication. As well as achieving therapy in preclinical models of HCC through the activation of innate degranulating immune cells, Reo-induced cytokine responses efficiently suppressed HCV replication both in vitro and in vivo. Furthermore, Reo-induced innate responses were also effective against models of HBV-associated HCC, as well as an alternative endogenous model of Epstein–Barr virus-associated lymphoma. Interestingly, Reo appeared superior to the majority of OVs in its ability to elicit innate inflammatory responses from primary liver tissue. Conclusions: We propose that Reo and other select proinflammatory OV may be used in the treatment of multiple cancers associated with oncogenic virus infections, simultaneously reducing both virus-associated oncogenic drive and tumour burden. In the case of HCV-associated HCC (HCV-HCC), Reo should be considered as an alternative agent to supplement and support current HCV-HCC therapies, particularly in those countries where access to new HCV antiviral treatments may be limited.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Editors: |
|
Copyright, Publisher and Additional Information: | This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/ |
Keywords: | Oncolytic virus; immunotherapy; hepatitis C virus; hepatocellular carcinoma; Reovirus |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) |
Depositing User: | Symplectic Publications |
Date Deposited: | 18 Oct 2016 10:09 |
Last Modified: | 23 Jun 2023 22:15 |
Status: | Published |
Publisher: | BMJ Publishing Group |
Identification Number: | 10.1136/gutjnl-2016-312009 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:106039 |