Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer.
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Date
2018-03-01Author
Samson, A
Bentham, MJ
Scott, K
Nuovo, G
Bloy, A
Appleton, E
Adair, RA
Dave, R
Peckham-Cooper, A
Toogood, G
Nagamori, S
Coffey, M
Vile, R
Harrington, K
Selby, P
Errington-Mais, F
Melcher, A
Griffin, S
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Liver
Leukocytes, Mononuclear
Cell Line, Tumor
Hepatocytes
Animals
Humans
Mice
Mice, SCID
Herpesvirus 4, Human
Hepacivirus
Reoviridae
Burkitt Lymphoma
Carcinoma, Hepatocellular
Liver Neoplasms
Interferons
Interferon-alpha
Interferon-beta
Interleukins
Culture Media, Conditioned
Xenograft Model Antitumor Assays
Virus Replication
Oncolytic Virotherapy
Oncolytic Viruses
Immunity, Innate
Natural Killer T-Cells
Research team
Translational Immunotherapy
Language
eng
Date accepted
2016-10-13
License start date
2018-03
Citation
Gut, 2018, 67 (3), pp. 562 - 573
Publisher
BMJ PUBLISHING GROUP