A Multi Targeting Conditionally Replicating Adenovirus Displays Enhanced Oncolysis while Maintaining Expression of Immunotherapeutic Agents

Studies have demonstrated that oncolytic adenoviruses based on a 24 base pair deletion in the viral E1A gene (D24) may be promising therapeutics for treating a number of cancer types. In order to increase the therapeutic potential of these oncolytic viruses, a novel conditionally replicating adenovi...

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Autores principales: Dobbins, G. Clement, Ugai, Hideyo, Curiel, David T., Gillespie, G. Yancey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687127/
https://www.ncbi.nlm.nih.gov/pubmed/26689910
http://dx.doi.org/10.1371/journal.pone.0145272
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author Dobbins, G. Clement
Ugai, Hideyo
Curiel, David T.
Gillespie, G. Yancey
author_facet Dobbins, G. Clement
Ugai, Hideyo
Curiel, David T.
Gillespie, G. Yancey
author_sort Dobbins, G. Clement
collection PubMed
description Studies have demonstrated that oncolytic adenoviruses based on a 24 base pair deletion in the viral E1A gene (D24) may be promising therapeutics for treating a number of cancer types. In order to increase the therapeutic potential of these oncolytic viruses, a novel conditionally replicating adenovirus targeting multiple receptors upregulated on tumors was generated by incorporating an Ad5/3 fiber with a carboxyl terminus RGD ligand. The virus displayed full cytopathic effect in all tumor lines assayed at low titers with improved cytotoxicity over Ad5-RGD D24, Ad5/3 D24 and an HSV oncolytic virus. The virus was then engineered to deliver immunotherapeutic agents such as GM-CSF while maintaining enhanced heterogenic oncolysis.
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spelling pubmed-46871272016-01-07 A Multi Targeting Conditionally Replicating Adenovirus Displays Enhanced Oncolysis while Maintaining Expression of Immunotherapeutic Agents Dobbins, G. Clement Ugai, Hideyo Curiel, David T. Gillespie, G. Yancey PLoS One Research Article Studies have demonstrated that oncolytic adenoviruses based on a 24 base pair deletion in the viral E1A gene (D24) may be promising therapeutics for treating a number of cancer types. In order to increase the therapeutic potential of these oncolytic viruses, a novel conditionally replicating adenovirus targeting multiple receptors upregulated on tumors was generated by incorporating an Ad5/3 fiber with a carboxyl terminus RGD ligand. The virus displayed full cytopathic effect in all tumor lines assayed at low titers with improved cytotoxicity over Ad5-RGD D24, Ad5/3 D24 and an HSV oncolytic virus. The virus was then engineered to deliver immunotherapeutic agents such as GM-CSF while maintaining enhanced heterogenic oncolysis. Public Library of Science 2015-12-21 /pmc/articles/PMC4687127/ /pubmed/26689910 http://dx.doi.org/10.1371/journal.pone.0145272 Text en © 2015 Dobbins et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Dobbins, G. Clement
Ugai, Hideyo
Curiel, David T.
Gillespie, G. Yancey
A Multi Targeting Conditionally Replicating Adenovirus Displays Enhanced Oncolysis while Maintaining Expression of Immunotherapeutic Agents
title A Multi Targeting Conditionally Replicating Adenovirus Displays Enhanced Oncolysis while Maintaining Expression of Immunotherapeutic Agents
title_full A Multi Targeting Conditionally Replicating Adenovirus Displays Enhanced Oncolysis while Maintaining Expression of Immunotherapeutic Agents
title_fullStr A Multi Targeting Conditionally Replicating Adenovirus Displays Enhanced Oncolysis while Maintaining Expression of Immunotherapeutic Agents
title_full_unstemmed A Multi Targeting Conditionally Replicating Adenovirus Displays Enhanced Oncolysis while Maintaining Expression of Immunotherapeutic Agents
title_short A Multi Targeting Conditionally Replicating Adenovirus Displays Enhanced Oncolysis while Maintaining Expression of Immunotherapeutic Agents
title_sort multi targeting conditionally replicating adenovirus displays enhanced oncolysis while maintaining expression of immunotherapeutic agents
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687127/
https://www.ncbi.nlm.nih.gov/pubmed/26689910
http://dx.doi.org/10.1371/journal.pone.0145272
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