dc.contributor.author | Jennings, VA | |
dc.contributor.author | Scott, GB | |
dc.contributor.author | Rose, AMS | |
dc.contributor.author | Scott, KJ | |
dc.contributor.author | Migneco, G | |
dc.contributor.author | Keller, B | |
dc.contributor.author | Reilly, K | |
dc.contributor.author | Donnelly, O | |
dc.contributor.author | Peach, H | |
dc.contributor.author | Dewar, D | |
dc.contributor.author | Harrington, KJ | |
dc.contributor.author | Pandha, H | |
dc.contributor.author | Samson, A | |
dc.contributor.author | Vile, RG | |
dc.contributor.author | Melcher, AA | |
dc.contributor.author | Errington-Mais, F | |
dc.date.accessioned | 2019-06-19T15:14:28Z | |
dc.date.issued | 2019-06-05 | |
dc.identifier.citation | Molecular therapy : the journal of the American Society of Gene Therapy, 2019, 27 (6), pp. 1139 - 1152 | |
dc.identifier.issn | 1525-0016 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3261 | |
dc.identifier.eissn | 1525-0024 | |
dc.identifier.doi | 10.1016/j.ymthe.2019.04.008 | |
dc.description.abstract | 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 (HSVGM-CSF) alone and in combination with histone deacetylase inhibition. We found that HSVGM-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 HSVGM-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. | |
dc.format | Print-Electronic | |
dc.format.extent | 1139 - 1152 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Dendritic Cells | |
dc.subject | Killer Cells, Natural | |
dc.subject | T-Lymphocytes, Cytotoxic | |
dc.subject | Humans | |
dc.subject | Simplexvirus | |
dc.subject | Herpesvirus 1, Human | |
dc.subject | Melanoma | |
dc.subject | Skin Neoplasms | |
dc.subject | Valproic Acid | |
dc.subject | Granulocyte-Macrophage Colony-Stimulating Factor | |
dc.subject | Interferon Type I | |
dc.subject | Biological Products | |
dc.subject | Antigens, Neoplasm | |
dc.subject | Drug Therapy, Combination | |
dc.subject | Cell Survival | |
dc.subject | Genetic Vectors | |
dc.subject | Oncolytic Virotherapy | |
dc.subject | Oncolytic Viruses | |
dc.subject | Histone Deacetylase Inhibitors | |
dc.subject | MCF-7 Cells | |
dc.subject | Antineoplastic Agents, Immunological | |
dc.title | Potentiating Oncolytic Virus-Induced Immune-Mediated Tumor Cell Killing Using Histone Deacetylase Inhibition. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-04-08 | |
rioxxterms.versionofrecord | 10.1016/j.ymthe.2019.04.008 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-06 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Molecular therapy : the journal of the American Society of Gene Therapy | |
pubs.issue | 6 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy/Translational Immunotherapy (TL) | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy/Translational Immunotherapy (TL) | |
pubs.publication-status | Published | |
pubs.volume | 27 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Targeted Therapy | |
icr.researchteam | Translational Immunotherapy | |
dc.contributor.icrauthor | Harrington, Kevin | |
dc.contributor.icrauthor | Melcher, Alan | |