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  • Review Article
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Oncolytic virotherapy for urological cancers

Nature Reviews Urology volume 13, pages 334–352 (2016)Cite this article

Subjects

Key Points

  • Oncolytic virotherapy is a cancer treatment that employs replication-competent viruses, which specifically infect, replicate in and lyse malignant tumour cells, while minimizing harm to normal cells

  • Several oncolytic agents have been investigated in clinical trials in patients with urological cancers, demonstrating a number of challenges to their effectiveness and a need to improve their safety

  • Innate and adaptive virus-targeted immune responses, loss of viruses in tumour- associated tissues and suboptimal virus replication hamper the effectiveness of virotherapy

  • Current developments take into account distinctive features of urological tumours, for example by exploiting genetic alterations, such as changed expression levels of oncogenes, tumour suppressor genes and receptors

  • The strategies employed to improve oncolytic effectiveness and safety include alteration of virus tropism, regulating viral gene expression, arming viruses with immunostimulatory factors and combination with chemotherapy and radiotherapy

Abstract

Oncolytic virotherapy is a cancer treatment in which replication-competent viruses are used that specifically infect, replicate in and lyse malignant tumour cells, while minimizing harm to normal cells. Anecdotal evidence of the effectiveness of this strategy has existed since the late nineteenth century, but advances and innovations in biotechnological methods in the 1980s and 1990s led to a renewed interest in this type of therapy. Multiple clinical trials investigating the use of agents constructed from a wide range of viruses have since been performed, and several of these enrolled patients with urological malignancies. Data from these clinical trials and from preclinical studies revealed a number of challenges to the effectiveness of oncolytic virotherapy that have prompted the development of further sophisticated strategies. Urological cancers have a range of distinctive features, such as specific genetic mutations and cell surface markers, which enable improving both effectiveness and safety of oncolytic virus treatments. The strategies employed in creating advanced oncolytic agents include alteration of the virus tropism, regulating transcription and translation of viral genes, combination with chemotherapy, radiotherapy or gene therapy, arming viruses with factors that stimulate the immune response against tumour cells and delivery technologies to ensure that the viral agent reaches its target tissue.

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Authors and Affiliations

  1. Department of Surgery, University of British Columbia, 2211 Wesbrook Mall, Vancouver, V6T 2B5, British Columbia, Canada

    Zahid Delwar & William Jia

  2. Department of Urology, University of British Columbia, Level 6, 2775 Laurel Street, Vancouver, V5Z 1M9, British Columbia, Canada

    Kaixin Zhang

  3. Prostate Research Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, V6H 3Z6, British Columbia, Canada

    Paul S. Rennie

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Z.D., K.Z., P.S.R. and W.J. researched data for the article and made substantial contributions to the discussion of its content. Z.D., K.Z. and W.J. wrote the article. P.S.R. and W.J. reviewed and/or edited the manuscript before submission. Z.D. and K.Z. contributed equally to the preparation of this article.

Corresponding author

Correspondence to William Jia.

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Competing interests

W.J. is a founder and director of Virogin Biotech Ltd, a company developing oncolytic viruses for cancer treatment. Z.D., K.Z. and P.S.R. declare no competing interests.

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Delwar, Z., Zhang, K., Rennie, P. et al. Oncolytic virotherapy for urological cancers. Nat Rev Urol 13, 334–352 (2016). https://doi.org/10.1038/nrurol.2016.84

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