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High-throughput screening to enhance oncolytic virus immunotherapy

Authors Allan K, Stojdl D, Swift S

Received 3 October 2015

Accepted for publication 14 January 2016

Published 5 April 2016 Volume 2016:5 Pages 15—25

DOI https://doi.org/10.2147/OV.S66217

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Honey Reddi

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati


KJ Allan,1,2 David F Stojdl,1–3 SL Swift1

1Children’s Hospital of Eastern Ontario (CHEO) Research Institute, 2Department of Biology, Microbiology and Immunology, 3Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada

Abstract: High-throughput screens can rapidly scan and capture large amounts of information across multiple biological parameters. Although many screens have been designed to uncover potential new therapeutic targets capable of crippling viruses that cause disease, there have been relatively few directed at improving the efficacy of viruses that are used to treat disease. Oncolytic viruses (OVs) are biotherapeutic agents with an inherent specificity for treating malignant disease. Certain OV platforms – including those based on herpes simplex virus, reovirus, and vaccinia virus – have shown success against solid tumors in advanced clinical trials. Yet, many of these OVs have only undergone minimal engineering to solidify tumor specificity, with few extra modifications to manipulate additional factors. Several aspects of the interaction between an OV and a tumor-bearing host have clear value as targets to improve therapeutic outcomes. At the virus level, these include delivery to the tumor, infectivity, productivity, oncolysis, bystander killing, spread, and persistence. At the host level, these include engaging the immune system and manipulating the tumor microenvironment. Here, we review the chemical- and genome-based high-throughput screens that have been performed to manipulate such parameters during OV infection and analyze their impact on therapeutic efficacy. We further explore emerging themes that represent key areas of focus for future research.

Keywords: oncolytic, virus, screen, high-throughput, cancer, chemical, genomic, immunotherapy

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