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dc.contributor.authorComins, Cen_US
dc.contributor.authorSimpson, GRen_US
dc.contributor.authorRogers, Wen_US
dc.contributor.authorRelph, Ken_US
dc.contributor.authorHarrington, Ken_US
dc.contributor.authorMelcher, Aen_US
dc.contributor.authorRoulstone, Ven_US
dc.contributor.authorKyula, Jen_US
dc.contributor.authorPandha, Hen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2018-05-21T10:09:11Z
dc.date.issued2018-06en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29720674en_US
dc.identifier10.1038/s41417-018-0011-8en_US
dc.identifier.citationCancer Gene Ther, 2018, 25 (5-6), pp. 148 - 160en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1676
dc.identifier.eissn1476-5500en_US
dc.identifier.doi10.1038/s41417-018-0011-8en_US
dc.description.abstractThere are currently numerous oncolytic viruses undergoing clinical trial evaluation in cancer patients and one agent, Talimogene laherparepvec, has been approved for the treatment of malignant melanoma. This progress highlights the huge clinical potential of this treatment modality, and the focus is now combining these agents with conventional anticancer treatments or agents that enhance viral replication, and thereby oncolysis, in the tumour microenvironment. We evaluated the combination of reovirus with rapamycin in B16F10 cell, a murine model of malignant melanoma, based on potential mechanisms by which mTOR inhibitors might enhance viral oncolysis. Rapamycin was not immunomodulatory in that it had no effect on the generation of an antireovirus-neutralising antibody response in C57/black 6 mice. The cell cycle effects of reovirus (increase G0/G1 fraction) were unaffected by concomitant or sequential exposure of rapamycin. However, rapamycin attenuated viral replication if given prior or concomitantly with reovirus and similarly reduced reovirus-induced apoptotic cell death Annexin V/PI and caspase 3/7 activation studies. We found clear evidence of synergistic antitumour effects of the combination both in vitro and in vivo, which was sequence dependent only in the in vitro setting. In conclusion, we have demonstrated synergistic antitumour efficacy of reovirus and rapamycin combination.en_US
dc.format.extent148 - 160en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.titleSynergistic antitumour effects of rapamycin and oncolytic reovirus.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-08-31en_US
rioxxterms.versionofrecord10.1038/s41417-018-0011-8en_US
rioxxterms.licenseref.startdate2018-06en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfCancer Gene Theren_US
pubs.issue5-6en_US
pubs.notesNot knownen_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/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.publication-statusPublisheden_US
pubs.volume25en_US
pubs.embargo.termsNot knownen_US
icr.researchteamTargeted Therapyen_US
dc.contributor.icrauthorHarrington, Kevinen_US


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