dc.contributor.author | Kottke, T | |
dc.contributor.author | Tonne, J | |
dc.contributor.author | Evgin, L | |
dc.contributor.author | Driscoll, CB | |
dc.contributor.author | van Vloten, J | |
dc.contributor.author | Jennings, VA | |
dc.contributor.author | Huff, AL | |
dc.contributor.author | Zell, B | |
dc.contributor.author | Thompson, JM | |
dc.contributor.author | Wongthida, P | |
dc.contributor.author | Pulido, J | |
dc.contributor.author | Schuelke, MR | |
dc.contributor.author | Samson, A | |
dc.contributor.author | Selby, P | |
dc.contributor.author | Ilett, E | |
dc.contributor.author | McNiven, M | |
dc.contributor.author | Roberts, LR | |
dc.contributor.author | Borad, MJ | |
dc.contributor.author | Pandha, H | |
dc.contributor.author | Harrington, K | |
dc.contributor.author | Melcher, A | |
dc.contributor.author | Vile, RG | |
dc.date.accessioned | 2021-04-13T10:18:08Z | |
dc.date.available | 2021-04-13T10:18:08Z | |
dc.date.issued | 2021-03-26 | |
dc.identifier.citation | Nature communications, 2021, 12 (1), pp. 1930 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4519 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-021-22115-1 | |
dc.description.abstract | In 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 CSDE1P5S 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 CSDE1P5S cells. These data show that CSDE1 is a major cellular co-factor for VSV replication. However, CSDE1P5S 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 CSDE1P5S, 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.format | Electronic | |
dc.format.extent | 1930 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Oncolytic virotherapy induced CSDE1 neo-antigenesis restricts VSV replication but can be targeted by immunotherapy. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-02-25 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41467-021-22115-1 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-03-26 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.issue | 1 | |
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/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-status | Published | |
pubs.volume | 12 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Targeted Therapy | |
icr.researchteam | Targeted Therapy | |
dc.contributor.icrauthor | Harrington, Kevin | |
dc.contributor.icrauthor | Melcher, Alan | |