dc.contributor.author | Smith, HG | |
dc.contributor.author | Mansfield, D | |
dc.contributor.author | Roulstone, V | |
dc.contributor.author | Kyula-Currie, JN | |
dc.contributor.author | McLaughlin, M | |
dc.contributor.author | Patel, RR | |
dc.contributor.author | Bergerhoff, KF | |
dc.contributor.author | Paget, JT | |
dc.contributor.author | Dillon, MT | |
dc.contributor.author | Khan, A | |
dc.contributor.author | Melcher, A | |
dc.contributor.author | Thway, K | |
dc.contributor.author | Harrington, KJ | |
dc.contributor.author | Hayes, AJ | |
dc.date.accessioned | 2019-03-26T11:04:28Z | |
dc.date.issued | 2019-06-01 | |
dc.identifier.citation | Clinical cancer research : an official journal of the American Association for Cancer Research, 2019, 25 (11), pp. 3443 - 3454 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3160 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.ccr-18-3767 | |
dc.description.abstract | PURPOSE: The prevention and treatment of metastatic sarcoma are areas of significant unmet need. Immune checkpoint inhibitor monotherapy has shown little activity in sarcoma and there is great interest in identifying novel treatment combinations that may augment responses. In vitro and in vivo, we investigated the potential for an oncolytic vaccinia virus (GLV-1h68) delivered using isolated limb perfusion (ILP) to promote antitumor immune responses and augment response to PD-1 blockade in sarcoma.Experimental Design: In an established animal model of extremity sarcoma, we evaluated the potential of locoregional delivery of a vaccinia virus (GLV-1h68) alongside biochemotherapy (melphalan/TNFα) in ILP. Complementary in vitro assays for markers of immunogenic cell death were performed in sarcoma cell lines. RESULTS: PD-1 monotherapy had minimal efficacy in vivo, mimicking the clinical scenario. Pretreatment with GLV-1h68 delivered by ILP (viral ILP) significantly improved responses. Furthermore, when performed prior to surgery and radiotherapy, viral ILP and PD-1 blockade prevented both local and distant relapse, curing a previously treatment-refractory model. Enhanced therapy was associated with marked modulation of the tumor microenvironment, with an increase in the number and penetrance of intratumoral CD8+ T cells and expansion and activation of dendritic cells. GLV-1h68 was capable of inducing markers of immunogenic cell death in human sarcoma cell lines. CONCLUSIONS: Viral ILP augments the response to PD-1 blockade, transforming this locoregional therapy into a potentially effective systemic treatment for sarcoma and warrants translational evaluation. | |
dc.format | Print-Electronic | |
dc.format.extent | 3443 - 3454 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.rights.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
dc.subject | T-Lymphocyte Subsets | |
dc.subject | Lymphocytes, Tumor-Infiltrating | |
dc.subject | Cell Line, Tumor | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Vaccinia virus | |
dc.subject | Sarcoma | |
dc.subject | Disease Models, Animal | |
dc.subject | Treatment Outcome | |
dc.subject | Immunohistochemistry | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.subject | Immunophenotyping | |
dc.subject | Oncolytic Virotherapy | |
dc.subject | Oncolytic Viruses | |
dc.subject | Programmed Cell Death 1 Receptor | |
dc.subject | Genetic Therapy | |
dc.subject | Antineoplastic Agents, Immunological | |
dc.title | PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-03-08 | |
rioxxterms.versionofrecord | 10.1158/1078-0432.ccr-18-3767 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
rioxxterms.licenseref.startdate | 2019-06 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Clinical cancer research : an official journal of the American Association for Cancer Research | |
pubs.issue | 11 | |
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/Sarcoma and Melanoma Surgery | |
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/Sarcoma and Melanoma Surgery | |
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 | 25 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Sarcoma and Melanoma Surgery | |
icr.researchteam | Targeted Therapy | |
icr.researchteam | Translational Immunotherapy | |
dc.contributor.icrauthor | Mansfield, David | |
dc.contributor.icrauthor | Roulstone, Victoria | |
dc.contributor.icrauthor | McLaughlin, Martin | |
dc.contributor.icrauthor | Dillon, Magnus | |
dc.contributor.icrauthor | Melcher, Alan | |
dc.contributor.icrauthor | Harrington, Kevin | |