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High-throughput screening to enhance oncolytic virus immunotherapy

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 i...

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Detalles Bibliográficos
Autores principales: Allan, KJ, Stojdl, David F, Swift, SL
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996253/
https://www.ncbi.nlm.nih.gov/pubmed/27579293
http://dx.doi.org/10.2147/OV.S66217
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author Allan, KJ
Stojdl, David F
Swift, SL
author_facet Allan, KJ
Stojdl, David F
Swift, SL
author_sort Allan, KJ
collection PubMed
description 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.
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spelling pubmed-49962532016-08-30 High-throughput screening to enhance oncolytic virus immunotherapy Allan, KJ Stojdl, David F Swift, SL Oncolytic Virother Review 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. Dove Medical Press 2016-04-05 /pmc/articles/PMC4996253/ /pubmed/27579293 http://dx.doi.org/10.2147/OV.S66217 Text en © 2016 Allan et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Review
Allan, KJ
Stojdl, David F
Swift, SL
High-throughput screening to enhance oncolytic virus immunotherapy
title High-throughput screening to enhance oncolytic virus immunotherapy
title_full High-throughput screening to enhance oncolytic virus immunotherapy
title_fullStr High-throughput screening to enhance oncolytic virus immunotherapy
title_full_unstemmed High-throughput screening to enhance oncolytic virus immunotherapy
title_short High-throughput screening to enhance oncolytic virus immunotherapy
title_sort high-throughput screening to enhance oncolytic virus immunotherapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996253/
https://www.ncbi.nlm.nih.gov/pubmed/27579293
http://dx.doi.org/10.2147/OV.S66217
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