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Potentiating Oncolytic Virus-Induced Immune-Mediated Tumor Cell Killing Using Histone Deacetylase Inhibition
A clinical oncolytic herpes simplex virus (HSV) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), talimogene laherparepvec, causes regression of injected and non-injected melanoma lesions in patients and is now licensed for clinical use in advanced melanoma. To date, limited data a...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554638/ https://www.ncbi.nlm.nih.gov/pubmed/31053413 http://dx.doi.org/10.1016/j.ymthe.2019.04.008 |
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author | Jennings, Victoria A. Scott, Gina B. Rose, Ailsa M.S. Scott, Karen J. Migneco, Gemma Keller, Brian Reilly, Katrina Donnelly, Oliver Peach, Howard Dewar, Donald Harrington, Kevin J. Pandha, Hardev Samson, Adel Vile, Richard G. Melcher, Alan A. Errington-Mais, Fiona |
author_facet | Jennings, Victoria A. Scott, Gina B. Rose, Ailsa M.S. Scott, Karen J. Migneco, Gemma Keller, Brian Reilly, Katrina Donnelly, Oliver Peach, Howard Dewar, Donald Harrington, Kevin J. Pandha, Hardev Samson, Adel Vile, Richard G. Melcher, Alan A. Errington-Mais, Fiona |
author_sort | Jennings, Victoria A. |
collection | PubMed |
description | A clinical oncolytic herpes simplex virus (HSV) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), talimogene laherparepvec, causes regression of injected and non-injected melanoma lesions in patients and is now licensed for clinical use in advanced melanoma. To date, limited data are available regarding the mechanisms of human anti-tumor immune priming, an improved understanding of which could inform the development of future combination strategies with improved efficacy. This study addressed direct oncolysis and innate and adaptive human immune-mediated effects of a closely related HSV encoding GM-CSF (HSV(GM-CSF)) alone and in combination with histone deacetylase inhibition. We found that HSV(GM-CSF) supported activation of anti-melanoma immunity via monocyte-mediated type I interferon production, which activates NK cells, and viral maturation of immature dendritic cells (iDCs) into potent antigen-presenting cells for cytotoxic T lymphocyte (CTL) priming. Addition of the histone deacetylase inhibitor valproic acid (VPA) to HSV(GM-CSF) treatment of tumor cells increased viral replication, viral GM-CSF production, and oncolysis and augmented the development of anti-tumor immunity. Mechanistically, VPA increased expression of activating ligands for NK cell recognition and induced expression of tumor-associated antigens, supporting innate NK cell killing and CTL priming. These data support the clinical combination of talimogene laherparepvec with histone deacetylase inhibition to enhance oncolysis and anti-tumor immunity. |
format | Online Article Text |
id | pubmed-6554638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-65546382019-07-11 Potentiating Oncolytic Virus-Induced Immune-Mediated Tumor Cell Killing Using Histone Deacetylase Inhibition Jennings, Victoria A. Scott, Gina B. Rose, Ailsa M.S. Scott, Karen J. Migneco, Gemma Keller, Brian Reilly, Katrina Donnelly, Oliver Peach, Howard Dewar, Donald Harrington, Kevin J. Pandha, Hardev Samson, Adel Vile, Richard G. Melcher, Alan A. Errington-Mais, Fiona Mol Ther Original Article A clinical oncolytic herpes simplex virus (HSV) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), talimogene laherparepvec, causes regression of injected and non-injected melanoma lesions in patients and is now licensed for clinical use in advanced melanoma. To date, limited data are available regarding the mechanisms of human anti-tumor immune priming, an improved understanding of which could inform the development of future combination strategies with improved efficacy. This study addressed direct oncolysis and innate and adaptive human immune-mediated effects of a closely related HSV encoding GM-CSF (HSV(GM-CSF)) alone and in combination with histone deacetylase inhibition. We found that HSV(GM-CSF) supported activation of anti-melanoma immunity via monocyte-mediated type I interferon production, which activates NK cells, and viral maturation of immature dendritic cells (iDCs) into potent antigen-presenting cells for cytotoxic T lymphocyte (CTL) priming. Addition of the histone deacetylase inhibitor valproic acid (VPA) to HSV(GM-CSF) treatment of tumor cells increased viral replication, viral GM-CSF production, and oncolysis and augmented the development of anti-tumor immunity. Mechanistically, VPA increased expression of activating ligands for NK cell recognition and induced expression of tumor-associated antigens, supporting innate NK cell killing and CTL priming. These data support the clinical combination of talimogene laherparepvec with histone deacetylase inhibition to enhance oncolysis and anti-tumor immunity. American Society of Gene & Cell Therapy 2019-06-05 2019-04-14 /pmc/articles/PMC6554638/ /pubmed/31053413 http://dx.doi.org/10.1016/j.ymthe.2019.04.008 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Article Jennings, Victoria A. Scott, Gina B. Rose, Ailsa M.S. Scott, Karen J. Migneco, Gemma Keller, Brian Reilly, Katrina Donnelly, Oliver Peach, Howard Dewar, Donald Harrington, Kevin J. Pandha, Hardev Samson, Adel Vile, Richard G. Melcher, Alan A. Errington-Mais, Fiona Potentiating Oncolytic Virus-Induced Immune-Mediated Tumor Cell Killing Using Histone Deacetylase Inhibition |
title | Potentiating Oncolytic Virus-Induced Immune-Mediated Tumor Cell Killing Using Histone Deacetylase Inhibition |
title_full | Potentiating Oncolytic Virus-Induced Immune-Mediated Tumor Cell Killing Using Histone Deacetylase Inhibition |
title_fullStr | Potentiating Oncolytic Virus-Induced Immune-Mediated Tumor Cell Killing Using Histone Deacetylase Inhibition |
title_full_unstemmed | Potentiating Oncolytic Virus-Induced Immune-Mediated Tumor Cell Killing Using Histone Deacetylase Inhibition |
title_short | Potentiating Oncolytic Virus-Induced Immune-Mediated Tumor Cell Killing Using Histone Deacetylase Inhibition |
title_sort | potentiating oncolytic virus-induced immune-mediated tumor cell killing using histone deacetylase inhibition |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554638/ https://www.ncbi.nlm.nih.gov/pubmed/31053413 http://dx.doi.org/10.1016/j.ymthe.2019.04.008 |
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