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dc.contributor.authorKottke, T
dc.contributor.authorTonne, J
dc.contributor.authorEvgin, L
dc.contributor.authorDriscoll, CB
dc.contributor.authorvan Vloten, J
dc.contributor.authorJennings, VA
dc.contributor.authorHuff, AL
dc.contributor.authorZell, B
dc.contributor.authorThompson, JM
dc.contributor.authorWongthida, P
dc.contributor.authorPulido, J
dc.contributor.authorSchuelke, MR
dc.contributor.authorSamson, A
dc.contributor.authorSelby, P
dc.contributor.authorIlett, E
dc.contributor.authorMcNiven, M
dc.contributor.authorRoberts, LR
dc.contributor.authorBorad, MJ
dc.contributor.authorPandha, H
dc.contributor.authorHarrington, K
dc.contributor.authorMelcher, A
dc.contributor.authorVile, RG
dc.date.accessioned2021-04-13T10:18:08Z
dc.date.available2021-04-13T10:18:08Z
dc.date.issued2021-03-26
dc.identifier.citationNature communications, 2021, 12 (1), pp. 1930 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4519
dc.identifier.eissn2041-1723
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/s41467-021-22115-1
dc.identifier.doi10.1038/s41467-021-22115-1en_US
dc.description.abstractIn our clinical trials of oncolytic vesicular stomatitis virus expressing interferon beta (VSV-IFNβ), several patients achieved initial responses followed by aggressive relapse. We show here that VSV-IFNβ-escape tumors predictably express a point-mutated CSDE1<sup>P5S</sup> form of the RNA-binding Cold Shock Domain-containing E1 protein, which promotes escape as an inhibitor of VSV replication by disrupting viral transcription. Given time, VSV-IFNβ evolves a compensatory mutation in the P/M Inter-Genic Region which rescues replication in CSDE1<sup>P5S</sup> cells. These data show that CSDE1 is a major cellular co-factor for VSV replication. However, CSDE1<sup>P5S</sup> also generates a neo-epitope recognized by non-tolerized T cells. We exploit this predictable neo-antigenesis to drive, and trap, tumors into an escape phenotype, which can be ambushed by vaccination against CSDE1<sup>P5S</sup>, preventing tumor escape. Combining frontline therapy with escape-targeting immunotherapy will be applicable across multiple therapies which drive tumor mutation/evolution and simultaneously generate novel, targetable immunopeptidomes associated with acquired treatment resistance.
dc.formatElectronic
dc.format.extent1930 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleOncolytic virotherapy induced CSDE1 neo-antigenesis restricts VSV replication but can be targeted by immunotherapy.
dc.typeJournal Article
dcterms.dateAccepted2021-02-25
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41467-021-22115-1
rioxxterms.licenseref.startdate2021-03-26
rioxxterms.licenseref.startdate2021-03-26en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.issue1
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
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-statusPublished
pubs.volume12en_US
pubs.embargo.termsNot known
icr.researchteamTargeted Therapy
icr.researchteamTargeted Therapyen_US
dc.contributor.icrauthorHarrington, Kevinen


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