dc.contributor.author | Kottke, T | |
dc.contributor.author | Shim, KG | |
dc.contributor.author | Alonso-Camino, V | |
dc.contributor.author | Zaidi, S | |
dc.contributor.author | Maria Diaz, R | |
dc.contributor.author | Pulido, J | |
dc.contributor.author | Thompson, J | |
dc.contributor.author | Rajani, KR | |
dc.contributor.author | Evgin, L | |
dc.contributor.author | Ilett, E | |
dc.contributor.author | Pandha, H | |
dc.contributor.author | Harrington, K | |
dc.contributor.author | Selby, P | |
dc.contributor.author | Melcher, A | |
dc.contributor.author | Vile, R | |
dc.date.accessioned | 2017-01-10T12:54:57Z | |
dc.date.issued | 2016-12-07 | |
dc.identifier.citation | Molecular therapy oncolytics, 2016, 3 pp. 16030 - ? | |
dc.identifier.issn | 2372-7705 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/384 | |
dc.identifier.eissn | 2372-7705 | |
dc.identifier.doi | 10.1038/mto.2016.30 | |
dc.description.abstract | We showed previously that therapy with Vesicular Stomatitis Virus (VSV) expressing tumor-associated proteins eradicates established tumors. We show here that when cellular cDNA were cloned into VSV which retained their own poly-A signal, viral species emerged in culture which had deleted the cellular poly-A signal and also contained a truncated form of the protein coding sequence. Typically, the truncation occurred such that a Tyrosine-encoding codon was converted into a STOP codon. We believe that the truncation of tumor-associated proteins expressed from VSV in this way occurred to preserve the ability of the virus to replicate efficiently. Truncated cDNA expressed from VSV were significantly more effective than full length cDNA in treating established tumors. Moreover, tumor therapy with truncated cDNA was completely abolished by depletion of CD4+ T cells, whereas therapy with full length cDNA was CD8+ T cell dependent. These data show that the type/potency of antitumor immune responses against self-tumor-associated proteins can be manipulated in vivo through the nature of the self protein (full length or truncated). Therefore, in addition to generation of neoantigens through sequence mutation, immunological tolerance against self-tumor-associated proteins can be broken through manipulation of protein integrity, allowing for rational design of better self-immunogens for cancer immunotherapy. | |
dc.format | Electronic-eCollection | |
dc.format.extent | 16030 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
dc.title | Immunogenicity of self tumor associated proteins is enhanced through protein truncation. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-10-15 | |
rioxxterms.versionofrecord | 10.1038/mto.2016.30 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2016-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Molecular therapy oncolytics | |
pubs.notes | No embargo | |
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-status | Published | |
pubs.volume | 3 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Targeted Therapy | |
icr.researchteam | Translational Immunotherapy | |
dc.contributor.icrauthor | Harrington, Kevin | |
dc.contributor.icrauthor | Melcher, Alan | |