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dc.contributor.authorMansfield, DCen_US
dc.contributor.authorKyula, JNen_US
dc.contributor.authorRosenfelder, Nen_US
dc.contributor.authorChao-Chu, Jen_US
dc.contributor.authorKramer-Marek, Gen_US
dc.contributor.authorKhan, AAen_US
dc.contributor.authorRoulstone, Ven_US
dc.contributor.authorMcLaughlin, Men_US
dc.contributor.authorMelcher, AAen_US
dc.contributor.authorVile, RGen_US
dc.contributor.authorPandha, HSen_US
dc.contributor.authorKhoo, Ven_US
dc.contributor.authorHarrington, KJen_US
dc.date.accessioned2016-08-16T14:55:51Z
dc.date.issued2016-04en_US
dc.identifier.citationGene therapy, 2016, 23 (4), pp. 357 - 368en_US
dc.identifier.issn0969-7128en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/48
dc.identifier.eissn1476-5462en_US
dc.identifier.doi10.1038/gt.2016.5en_US
dc.description.abstractOncolytic strains of vaccinia virus are currently in clinical development with clear evidence of safety and promising signs of efficacy. Addition of therapeutic genes to the viral genome may increase the therapeutic efficacy of vaccinia. We evaluated the therapeutic potential of vaccinia virus expressing the sodium iodide symporter (NIS) in prostate cancer models, combining oncolysis, external beam radiotherapy and NIS-mediated radioiodide therapy. The NIS-expressing vaccinia virus (VV-NIS), GLV-1h153, was tested in in vitro analyzes of viral cell killing, combination with radiotherapy, NIS expression, cellular radioiodide uptake and apoptotic cell death in PC3, DU145, LNCaP and WPMY-1 human prostate cell lines. In vivo experiments were carried out in PC3 xenografts in CD1 nude mice to assess NIS expression and tumor radioiodide uptake. In addition, the therapeutic benefit of radioiodide treatment in combination with viral oncolysis and external beam radiotherapy was measured. In vitro viral cell killing of prostate cancers was dose- and time-dependent and was through apoptotic mechanisms. Importantly, combined virus therapy and iodizing radiation did not adversely affect oncolysis. NIS gene expression in infected cells was functional and mediated uptake of radioiodide both in vitro and in vivo. Therapy experiments with both xenograft and immunocompetent Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse models showed that the addition of radioiodide to VV-NIS-infected tumors was more effective than each single-agent therapy, restricting tumor growth and increasing survival. In conclusion, VV-NIS is effective in prostate cancer models. This treatment modality would be an attractive complement to existing clinical radiotherapy practice.en_US
dc.formatPrint-Electronicen_US
dc.format.extent357 - 368en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectCell Line, Tumoren_US
dc.subjectAnimalsen_US
dc.subjectHumansen_US
dc.subjectMiceen_US
dc.subjectMice, Nudeen_US
dc.subjectVaccinia virusen_US
dc.subjectProstatic Neoplasmsen_US
dc.subjectSymportersen_US
dc.subjectRandom Allocationen_US
dc.subjectXenograft Model Antitumor Assaysen_US
dc.subjectTransfectionen_US
dc.subjectMaleen_US
dc.subjectOncolytic Virotherapyen_US
dc.subjectOncolytic Virusesen_US
dc.subjectGenetic Therapyen_US
dc.titleOncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-01-13en_US
rioxxterms.versionofrecord10.1038/gt.2016.5en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2016-04en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfGene therapyen_US
pubs.issue4en_US
pubs.notesNo embargoen_US
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Preclinical Molecular Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Preclinical Molecular 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/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume23en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamPreclinical Molecular Imagingen_US
icr.researchteamTargeted Therapyen_US
icr.researchteamTranslational Immunotherapyen_US
dc.contributor.icrauthorHarrington, Kevinen_US
dc.contributor.icrauthorMansfield, Daviden_US
dc.contributor.icrauthorKhoo, Vincenten_US
dc.contributor.icrauthorKramer-Marek, Gabrielaen_US
dc.contributor.icrauthorMelcher, Alanen_US
dc.contributor.icrauthorKhan, Aadilen_US
dc.contributor.icrauthorMcLaughlin, Martinen_US
dc.contributor.icrauthorRosenfelder, Nicolaen_US


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