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Original article
Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer
  1. Adel Samson1,
  2. Matthew J Bentham1,
  3. Karen Scott1,
  4. Gerard Nuovo2,
  5. Abigail Bloy1,
  6. Elizabeth Appleton1,
  7. Robert A Adair1,
  8. Rajiv Dave1,
  9. Adam Peckham-Cooper1,
  10. Giles Toogood1,
  11. Seishi Nagamori,
  12. Matthew Coffey3,4,
  13. Richard Vile1,5,6,
  14. Kevin Harrington6,
  15. Peter Selby1,
  16. Fiona Errington-Mais1,
  17. Alan Melcher6,
  18. Stephen Griffin1
  1. 1Leeds 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
  2. 2The Ohio State University, Comprehensive Cancer Centre, Columbus, Ohio, USA
  3. 3Department of Virology II, National Institute of Infectious Diseases 1-23-1 Toyama, Tokyo, Japan
  4. 4Oncolytics Biotech, Calgary, Alberta, Canada
  5. 5Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA
  6. 6Department of Molecular Medicine, The Institute of Cancer Research, London, UK
  1. Correspondence to Dr Stephen Griffin and Prof Alan Melcher, Faculty of Medicine and Health, Leeds Institute of Cancer & Pathology, University of Leeds, Wellcome Trust Brenner Building, St James’ University Hospital, Leeds LS7 9TF, UK; s.d.c.griffin{at}leeds.ac.uk and a.a.melcher{at}leeds.ac.uk

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.

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

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/

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Footnotes

  • AM and SG contributed equally.

  • Contributors Conceived and planned experiments: SG, AM, FE-M and AS; performed experiments: AS, MJB, KS, GN, AB, EA, RAA, RD and AP-C; provided key reagents: GT, SN and MC; reviewed manuscript: RV, KH, PS and FE-M; wrote manuscript: SG, AM and AS.

  • Funding AS was the recipient of a Cancer Research UK Clinical Fellowship awarded by the Cancer Research UK Leeds Centre to SG/AM.

  • Competing interests MC is an employee of Oncolytics Biotech, Calgary, Canada. SG and AM have received research grants from Oncolytics.

  • Ethics approval North East Leeds ethics committee, St. James’ University Hospital, Leeds, UK. In vivo animal models were approved by the University of Leeds local ethics review committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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