dc.contributor.author | Samson, A | |
dc.contributor.author | Bentham, MJ | |
dc.contributor.author | Scott, K | |
dc.contributor.author | Nuovo, G | |
dc.contributor.author | Bloy, A | |
dc.contributor.author | Appleton, E | |
dc.contributor.author | Adair, RA | |
dc.contributor.author | Dave, R | |
dc.contributor.author | Peckham-Cooper, A | |
dc.contributor.author | Toogood, G | |
dc.contributor.author | Nagamori, S | |
dc.contributor.author | Coffey, M | |
dc.contributor.author | Vile, R | |
dc.contributor.author | Harrington, K | |
dc.contributor.author | Selby, P | |
dc.contributor.author | Errington-Mais, F | |
dc.contributor.author | Melcher, A | |
dc.contributor.author | Griffin, S | |
dc.date.accessioned | 2017-03-01T12:12:00Z | |
dc.date.issued | 2018-03-01 | |
dc.identifier.citation | Gut, 2018, 67 (3), pp. 562 - 573 | |
dc.identifier.issn | 0017-5749 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/437 | |
dc.identifier.eissn | 1468-3288 | |
dc.identifier.doi | 10.1136/gutjnl-2016-312009 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.format.extent | 562 - 573 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | BMJ PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Liver | |
dc.subject | Leukocytes, Mononuclear | |
dc.subject | Cell Line, Tumor | |
dc.subject | Hepatocytes | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Mice, SCID | |
dc.subject | Herpesvirus 4, Human | |
dc.subject | Hepacivirus | |
dc.subject | Reoviridae | |
dc.subject | Burkitt Lymphoma | |
dc.subject | Carcinoma, Hepatocellular | |
dc.subject | Liver Neoplasms | |
dc.subject | Interferons | |
dc.subject | Interferon-alpha | |
dc.subject | Interferon-beta | |
dc.subject | Interleukins | |
dc.subject | Culture Media, Conditioned | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.subject | Virus Replication | |
dc.subject | Oncolytic Virotherapy | |
dc.subject | Oncolytic Viruses | |
dc.subject | Immunity, Innate | |
dc.subject | Natural Killer T-Cells | |
dc.title | Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-10-13 | |
rioxxterms.versionofrecord | 10.1136/gutjnl-2016-312009 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-03 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Gut | |
pubs.issue | 3 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy/Translational Immunotherapy (TL) | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy/Translational Immunotherapy (TL) | |
pubs.publication-status | Published | |
pubs.volume | 67 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Translational Immunotherapy | |
dc.contributor.icrauthor | Appleton, Elizabeth | |
dc.contributor.icrauthor | Harrington, Kevin | |
dc.contributor.icrauthor | Melcher, Alan | |