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  • Review Article
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New viruses for cancer therapy: meeting clinical needs

Nature Reviews Microbiology volume 12, pages 23–34 (2014)Cite this article

Subjects

Key Points

  • Oncolytic virotherapy re-engineers and repurposes replicating viruses for the treatment of cancer. Therapeutic viruses specifically infect and spread within cancer tissue, causing cell death.

  • In recent years, an increasing number of viruses have been developed as cancer therapeutics. There are nine virus families that are currently used in virotherapy clinical trials.

  • Different viruses have evolved tissue specificities that can be exploited to preferentially destroy certain tumour types.

  • Engineering strategies to improve the therapeutic potential of oncolytic viruses include protection from neutralizing immunity, restriction of entry or replication to tumour cells and expression of transgenes to synergize with traditional therapies and the anti-tumour activity of the patient's immune system.

  • Ion transport transgenes, such as the sodium–iodide symporter (NIS) can be used to image virus replication non-invasively at high resolutions using clinically available imaging technologies, such as single-photon emission computed tomography–computed tomography (SPECT–CT) and positron emission tomography (PET).

  • The individualization of therapy and our increasing knowledge of tumour pathophysiology will guide the application of engineered viruses against tumour types that have defined sensitivities to virotherapy.

Abstract

Early-stage clinical trials of oncolytic virotherapy have reported the safety of several virus platforms, and viruses from three families have progressed to advanced efficacy trials. In addition, preclinical studies have established proof-of-principle for many new genetic engineering strategies. Thus, the virotherapy field now has available a diverse collection of viruses that are equipped to address unmet clinical needs owing to improved systemic administration, greater tumour specificity and enhanced oncolytic efficacy. The current key challenge for the field is to develop viruses that replicate with greater efficiency within tumours while achieving therapeutic synergy with currently available treatments.

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Figure 1: Vector-shielding strategies.
Figure 2: Principles of tumour targeting — illustrated for four virus families.
Figure 3: Post-entry targeting.
Figure 4: Arming strategies that induce bystander cell killing.

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Acknowledgements

This work was supported by the US National Cancer Institute Grant R01 CA 139398. T.S.M's salary was supported in part by grant T32 GM065841 from the US National Institute of Health and US National Institute of General Medical Sciences.

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Authors and Affiliations

  1. Department of Molecular Medicine, Mayo Clinic, Rochester, 55905, Minnesota, USA

    Tanner S. Miest & Roberto Cattaneo

  2. Virology and Gene Therapy Track, Mayo Graduate School, Rochester, 55905, Minnesota, USA

    Tanner S. Miest & Roberto Cattaneo

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  1. Tanner S. Miest
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  2. Roberto Cattaneo
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Correspondence to Roberto Cattaneo.

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Glossary

Granulocyte–macrophage colony-stimulating factor

(GM-CSF). An immuno-stimulatory cytokine that functions as a growth factor for granulocytes and monocytes.

Serotype

A collection of viruses grouped according to common antigenic epitopes that are recognized by the same immune serum.

Coxsackie–adenovirus receptor

(CAR). An immunoglobulin-like transmembrane cell adhesion protein that is used by some coxsackievirus and adenovirus species as a receptor.

CD46

A ubiquitously expressed type-1 transmembrane protein that functions to regulate complement. It functions as a receptor for vaccine strains of measles virus and some adenovirus species.

Parenchyma

The bulk of tumours; consists of clonally transformed cells.

CD133+ cancer-initiating cells

A subset of tumour cells that have stem cell-like characteristics. They are capable of initiating new tumour growth and may drive tumour recurrence after therapy.

Prodrug

A chemotherapeutic drug that is dependent on enzymatic activation to achieve full activity.

Radioisotopes

Elements with unstable nuclei that emit γ-rays or α- or β-ionizing radiation.

Nucleoside analogues

Chemotherapeutic drugs that incorporate into replicating DNA as nucleosides but halt DNA replication, which leads to cell death.

γ-emitting isotopes

Radioactive isotopes that emit ionizing radiation in the form of high-energy electromagnetic γ rays.

β-emitting isotopes

Radioactive isotopes that emit ionizing radiation in the form of high-energy, high-speed electrons or protons.

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Miest, T., Cattaneo, R. New viruses for cancer therapy: meeting clinical needs. Nat Rev Microbiol 12, 23–34 (2014). https://doi.org/10.1038/nrmicro3140

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