Oncolytic virotherapy

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Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancers. Recent advances include preclinical proof of feasibility for a single-shot virotherapy cure, identification of drugs that accelerate intratumoral virus propagation, strategies to maximize the immunotherapeutic action of oncolytic viruses and clinical confirmation of a critical viremic threshold for vascular delivery and intratumoral virus replication. The primary clinical milestone has been completion of accrual in a phase 3 trial of intratumoral herpes simplex virus therapy using talimogene laherparepvec for metastatic melanoma. Key challenges for the field are to select 'winners' from a burgeoning number of oncolytic platforms and engineered derivatives, to transiently suppress but then unleash the power of the immune system to maximize both virus spread and anticancer immunity, to develop more meaningful preclinical virotherapy models and to manufacture viruses with orders-of-magnitude higher yields than is currently possible.

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Figure 1: A timeline of milestones in the development of oncolytic virotherapy to improve virus specificity, potency, delivery and spread.
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S.J.R. and K.-W.P. acknowledge funding support from the Mayo Foundation, Mayo Clinic Comprehensive Cancer Center (CA15083), US National Institutes of Health and National Cancer Institute (CA100634, CA129966, CA118488, CA129193, CA136547 and CA136393), Richard M. Schulze Family Foundation, Al and Mary Agnes McQuinn and Minnesota Partnership for Biotechnology. J.C.B. is supported by the Ontario Institute for Cancer Research, the Terry Fox Foundation and the Ottawa Regional Cancer Foundation.

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Correspondence to Stephen J Russell.

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J.C.B. is the chief scientific officer of Jennerex Biotherapeutics.

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Russell, S., Peng, K. & Bell, J. Oncolytic virotherapy. Nat Biotechnol 30, 658–670 (2012) doi:10.1038/nbt.2287

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