Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer

Adel Samson, Matthew J. Bentham, Karen Scott, Gerard Nuovo, Abigail Bloy, Elizabeth Appleton, Robert A. Adair, Rajiv Dave, Adam Peckham-Cooper, Giles Toogood, Seishi Nagamori, Matthew Coffey, Richard Vile, Kevin Harrington, Peter Selby, Fiona Errington-Mais, Alan Melcher, Stephen Griffin

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)562-573
Number of pages12
JournalGut
Volume67
Issue number3
DOIs
StatePublished - Mar 2018

Keywords

  • ANTIVIRAL THERAPY
  • CANCER IMMUNOBIOLOGY
  • HEPATITIS C
  • HEPATOCELLULAR CARCINOMA
  • IMMUNOTHERAPY

ASJC Scopus subject areas

  • Gastroenterology

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