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Oncolytic viruses: a novel form of immunotherapy

Robin J Prestwich, MD,† Kevin J Harrington, MD, PhD, Hardev S Pandha, MD, PhD, Richard G Vile, PhD, Alan A Melcher, MD, PhD, and Fiona Errington, PhD

Abstract

Oncolytic viruses are novel anticancer agents, currently under investigation in Phase I–III clinical trials. Until recently, most studies have focused on the direct antitumor properties of these viruses, although there is now an increasing body of evidence that the host immune response may be critical to the efficacy of oncolytic virotherapy. This may be mediated via innate immune effectors, adaptive antiviral immune responses eliminating infected cells or adaptive antitumor immune responses. This report summarizes preclinical and clinical evidence for the importance of immune interactions, which may be finely balanced between viral and tumor elimination. On this basis, oncolytic viruses represent a promising novel immunotherapy strategy, which may be optimally combined with existing therapeutic modalities.

Keywords: adaptive, clinical trial, immune response, immunotherapy, innate, oncolytic virus

The anticancer activity of viruses has been reported throughout the 20th century. Developments in virology, genetic manipulation and molecular biology have led to a surge of research investigating viruses with oncolytic or antitumor properties over the last 15 years. Several oncolytic viruses are currently in Phase I–III clinical trials [1]. Until recently, despite the multitude of studies investigating direct viral effects upon cancer cells, relatively little attention had been paid to the interaction between oncolytic viruses and the immune system. We discuss the evidence supporting the view that the host immune response is critical to the efficacy of oncolytic virotherapy. The potential of oncolytic viruses to break immunological tumor tolerance, generating antitumor immunity, represents a novel avenue of immunotherapy.

Figure 1

Concept of how oncolytic viral infection of tumor cells may lead to the generation of antitumor immune responses

Contributor Information

Robin J Prestwich, Cancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, LS9 7TF, UK, Tel.: +44 113 343 8450, Fax: +44 113 242 9886, Email: r.j.d.prestwich@leeds.ac.uk.

Kevin J Harrington, Targeted Therapy Laboratory, The Institute of Cancer Research, Cancer Research UK, Centre for Cell and Molecular Biology, Chester Beatty, Laboratories, 237 Fulham Road, London, SW3 6JB, UK, Tel.: +44 207 153 5157, Fax: +44 207 808 2235, Email: kevin.harrington@icr.ac.uk.

Hardev S Pandha, Oncology, Postgraduate Medical School, University of Surrey, Guildford, GU2 7XX, UK, Tel.: +44 148 368 8618, Fax: +44 148 368 8558, Email: h.pandha@surrey.ac.uk.

Richard G Vile, Cancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, LS9 7TF, UK; Molecular Medicine Program; Department of Immunology, Mayo Clinic, Rochester, Minnesota, 55905, USA, Tel.: +1 507 284 9941, Fax: +1 507 266 2122, Email: vile.richard@mayo.edu.

Alan A Melcher, Cancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, LS9 7TF, UK, Tel.: +44 113 343 8450, Fax: +44 113 242 9886, Email: a.a.melcher@surrey.ac.uk.

Fiona Errington, Cancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, LS9 7TF, UK, Tel.: +44 113 343 8450, Fax: +44 113 242 9886, Email: f.errington@leeds.ac.uk.

Taken from: NCBI

More Resources:

http://esciencenews.com/dictionary/oncolytic.viruses

http://www.cancer.gov/cancertopics/factsheet/Therapy/biological

http://www.ncbi.nlm.nih.gov/pubmed/11961194

http://dms.hms.harvard.edu/neuroscience/fac/Chiocca.php

http://www.ncbi.nlm.nih.gov/pubmed?term=Chiocca%20EA[Author]&cmd=DetailsSearch

http://www.dfhcc.harvard.edu/membership/profile/member/1492/0/

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http://www.dovepress.com/oncolytic-virotherapy-journal

http://www.jvir.org/article/S1051-0443%2813%2901024-5/abstract