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dc.contributor.authorComins, C
dc.contributor.authorSimpson, GR
dc.contributor.authorRogers, W
dc.contributor.authorRelph, K
dc.contributor.authorHarrington, K
dc.contributor.authorMelcher, A
dc.contributor.authorRoulstone, V
dc.contributor.authorKyula, J
dc.contributor.authorPandha, H
dc.date.accessioned2018-05-21T10:09:11Z
dc.date.issued2018-05-01
dc.identifier.citationCancer gene therapy, 2018, 25 (5-6), pp. 148 - 160
dc.identifier.issn0929-1903
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1676
dc.identifier.eissn1476-5500
dc.identifier.doi10.1038/s41417-018-0011-8
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.
dc.formatPrint-Electronic
dc.format.extent148 - 160
dc.languageeng
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectMice
dc.subjectMelanoma
dc.subjectSirolimus
dc.subjectOncolytic Virotherapy
dc.subjectOncolytic Viruses
dc.subjectMammalian orthoreovirus 3
dc.titleSynergistic antitumour effects of rapamycin and oncolytic reovirus.
dc.typeJournal Article
dcterms.dateAccepted2017-08-31
rioxxterms.versionofrecord10.1038/s41417-018-0011-8
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2018-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer gene therapy
pubs.issue5-6
pubs.notesNot 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-statusPublished
pubs.volume25
pubs.embargo.termsNot known
icr.researchteamTargeted Therapy
icr.researchteamTranslational Immunotherapy
dc.contributor.icrauthorHarrington, Kevin
dc.contributor.icrauthorMelcher, Alan
dc.contributor.icrauthorRoulstone, Victoria


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