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Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy

Oncolytic viruses (OV) are a class of antitumor agents that selectively kill tumor cells while sparing normal cells. Oncolytic herpes simplex virus (oHSV) has been investigated in clinical trials for patients with the malignant brain tumor glioblastoma for more than a decade. These clinical studies...

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Autores principales: Ning, Jianfang, Wakimoto, Hiroaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064532/
https://www.ncbi.nlm.nih.gov/pubmed/24999342
http://dx.doi.org/10.3389/fmicb.2014.00303
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author Ning, Jianfang
Wakimoto, Hiroaki
author_facet Ning, Jianfang
Wakimoto, Hiroaki
author_sort Ning, Jianfang
collection PubMed
description Oncolytic viruses (OV) are a class of antitumor agents that selectively kill tumor cells while sparing normal cells. Oncolytic herpes simplex virus (oHSV) has been investigated in clinical trials for patients with the malignant brain tumor glioblastoma for more than a decade. These clinical studies have shown the safety of oHSV administration to the human brain, however, therapeutic efficacy of oHSV as a single treatment remains unsatisfactory. Factors that could hamper the anti-glioblastoma efficacy of oHSV include: attenuated potency of oHSV due to deletion or mutation of viral genes involved in virulence, restricting viral replication and spread within the tumor; suboptimal oHSV delivery associated with intratumoral injection; virus infection-induced inflammatory and cellular immune responses which could inhibit oHSV replication and promote its clearance; lack of effective incorporation of oHSV into standard-of-care, and poor knowledge about the ability of oHSV to target glioblastoma stem cells (GSCs). In an attempt to address these issues, recent research efforts have been directed at: (1) design of new engineered viruses to enhance potency, (2) better understanding of the role of the cellular immunity elicited by oHSV infection of tumors, (3) combinatorial strategies with different antitumor agents with a mechanistic rationale, (4) “armed” viruses expressing therapeutic transgenes, (5) use of GSC-derived models in oHSV evaluation, and (6) combinations of these. In this review, we will describe the current status of oHSV clinical trials for glioblastoma, and discuss recent research advances and future directions toward successful oHSV-based therapy of glioblastoma.
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spelling pubmed-40645322014-07-04 Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy Ning, Jianfang Wakimoto, Hiroaki Front Microbiol Microbiology Oncolytic viruses (OV) are a class of antitumor agents that selectively kill tumor cells while sparing normal cells. Oncolytic herpes simplex virus (oHSV) has been investigated in clinical trials for patients with the malignant brain tumor glioblastoma for more than a decade. These clinical studies have shown the safety of oHSV administration to the human brain, however, therapeutic efficacy of oHSV as a single treatment remains unsatisfactory. Factors that could hamper the anti-glioblastoma efficacy of oHSV include: attenuated potency of oHSV due to deletion or mutation of viral genes involved in virulence, restricting viral replication and spread within the tumor; suboptimal oHSV delivery associated with intratumoral injection; virus infection-induced inflammatory and cellular immune responses which could inhibit oHSV replication and promote its clearance; lack of effective incorporation of oHSV into standard-of-care, and poor knowledge about the ability of oHSV to target glioblastoma stem cells (GSCs). In an attempt to address these issues, recent research efforts have been directed at: (1) design of new engineered viruses to enhance potency, (2) better understanding of the role of the cellular immunity elicited by oHSV infection of tumors, (3) combinatorial strategies with different antitumor agents with a mechanistic rationale, (4) “armed” viruses expressing therapeutic transgenes, (5) use of GSC-derived models in oHSV evaluation, and (6) combinations of these. In this review, we will describe the current status of oHSV clinical trials for glioblastoma, and discuss recent research advances and future directions toward successful oHSV-based therapy of glioblastoma. Frontiers Media S.A. 2014-06-20 /pmc/articles/PMC4064532/ /pubmed/24999342 http://dx.doi.org/10.3389/fmicb.2014.00303 Text en Copyright © 2014 Ning and Wakimoto. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Ning, Jianfang
Wakimoto, Hiroaki
Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy
title Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy
title_full Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy
title_fullStr Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy
title_full_unstemmed Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy
title_short Oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy
title_sort oncolytic herpes simplex virus-based strategies: toward a breakthrough in glioblastoma therapy
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4064532/
https://www.ncbi.nlm.nih.gov/pubmed/24999342
http://dx.doi.org/10.3389/fmicb.2014.00303
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