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Recent progress in the battle between oncolytic viruses and tumours

Key Points

  • Clinical trials have indicated that oncolytic viruses might be developed as safe and effective anticancer agents.

  • The translation of oncolytic viruses from the culture dish to preclinical tumour models to studies involving patients has revealed new hurdles to cancer therapy that can be overcome using multidisciplinary approaches.

  • Novel strategies can be used to facilitate viral evasion of the immune system, the prevention of viral uptake by the liver, and an increased specificity for tumour cells, either at the cell surface or through intracellular restriction.

  • Oncolytic viruses can be engineered to target the same genetic mutations that provide tumour cells with a proliferative or survival advantage in patients.

  • The intravenous delivery of viruses must be perfected if oncolytic virus-based therapeutics are to be used to treat patients with metastatic tumours.

Abstract

In the past 5 years, the field of oncolytic virus research has matured significantly and is moving past the stage of being a laboratory novelty into a new era of preclinical and clinical trials. What have recent anticancer trials of oncolytic viruses taught us about this exciting new line of therapeutics?

Figure 1: Infection and killing of tumour cells by an oncolytic virus.
Figure 2: Barriers to optimal delivery of oncolytic viruses to tumours in vivo.

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Acknowledgements

J.B. and P.F. are supported by grants from CIHR, NCIC, and the Terry Fox Foundation.

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Correspondence to John C. Bell.

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The authors declare no competing financial interests.

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DATABASES

Entrez Gene

CAR

CD46

EIF2α

MMP2

p53

PKR

RAS

SLAM

Entrez Genome

adenovirus type 5

measles virus

myxoma virus

Newcastle-disease virus

vaccinia virus

vesicular stomatitis virus

FURTHER INFORMATION

Adenovirus clinical trial

Reovirus clinical trial

Biovex herpes simplex virus clinical trial

Crusade laboratories herpes simplex virus clinical trial

Medigene herpes simplex virus clinical trials

Newcastle-disease virus clinical trial

Vaccinia virus information

Coxsackie virus information

Glossary

ENVELOPED AND NON-ENVELOPED VIRUSES

Broadly speaking, viruses can be subdivided into two groups: those that acquire a plasma membrane-derived envelope as they bud from an infected cell; or those that have only a protein coat and do not bud from the plasma membrane, but rather escape the infected cell following plasma membrane rupture.

IMMUNOLOGICAL MEMORY

The maintenance of an expanded number of circulating antigen-specific T- and B-lymphocytes, such that subsequent encounters with the same antigen are met with a more rapid immunological response.

ADJUVANT

Any compound that, when given simultaneously with antigen, increases the immunogenicity of that antigen, increasing the immune response.

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Parato, K., Senger, D., Forsyth, P. et al. Recent progress in the battle between oncolytic viruses and tumours. Nat Rev Cancer 5, 965–976 (2005). https://doi.org/10.1038/nrc1750

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