title: Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Leeds, UK.
authors.forename: Adel
authors.initials: A
authors.lastname: Samson
authors.affiliation: Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Leeds, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bentham
authors.affiliation: Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Leeds, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Scott
authors.affiliation: The Ohio State University, Comprehensive Cancer Centre, Columbus, Ohio, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Nuovo
authors.affiliation: Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Leeds, UK.
authors.forename: Abigail
authors.initials: A
authors.lastname: Bloy
authors.affiliation: Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Leeds, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Appleton
authors.affiliation: Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Leeds, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Adair
authors.affiliation: Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Leeds, UK.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Dave
authors.affiliation: Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Leeds, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Peckham-Cooper
authors.affiliation: Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Leeds, UK.
authors.forename: Giles
authors.initials: G
authors.lastname: Toogood
authors.forename: Seishi
authors.initials: S
authors.lastname: Nagamori
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases 1-23-1 Toyama, Tokyo, Japan.|Oncolytics Biotech, Calgary, Alberta, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Coffey
authors.affiliation: Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Leeds, UK.|Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.|Department of Molecular Medicine, The Institute of Cancer Research, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Vile
authors.affiliation: Department of Molecular Medicine, The Institute of Cancer Research, London, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Harrington
authors.affiliation: Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Leeds, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Selby
authors.affiliation: Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Leeds, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Errington-Mais
authors.affiliation: Department of Molecular Medicine, The Institute of Cancer Research, London, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Melcher
authors.affiliation: Leeds Institute of Cancer & Pathology (LICAP) and Leeds Cancer Research UK Clinical Centre, Faculty of Medicine and Health, University of Leeds, St James' University Hospital, Leeds, UK.
authors.forename: Stephen
authors.identifier: 0000-0002-7233-5243
authors.initials: S
authors.lastname: Griffin
mesh_terms: D000818:Animals; D002051:Burkitt Lymphoma / Q000276:immunology / Q000628:therapy / Q000821:virology; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy* / Q000821:virology; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016174:Hepacivirus / Q000276:immunology / Q000502:physiology*; D022781:Hepatocytes; D004854:Herpesvirus 4, Human; D006801:Humans; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000378:metabolism; D016899:Interferon-beta / Q000378:metabolism; D007372:Interferons; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear; D008099:Liver / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D055611:Natural Killer T-Cells / Q000276:immunology; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000276:immunology*; D012087:Reoviridae / Q000276:immunology*; D014779:Virus Replication / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000095022:Interferon Lambda
chemical_list: D017077:Culture Media, Conditioned; D016898:Interferon-alpha; D016899:Interferon-beta; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: ANTIVIRAL THERAPY; CANCER IMMUNOBIOLOGY; HEPATITIS C; HEPATOCELLULAR CARCINOMA; IMMUNOTHERAPY