dc.contributor.author | Driscoll, CB | |
dc.contributor.author | Schuelke, MR | |
dc.contributor.author | Kottke, T | |
dc.contributor.author | Thompson, JM | |
dc.contributor.author | Wongthida, P | |
dc.contributor.author | Tonne, JM | |
dc.contributor.author | Huff, AL | |
dc.contributor.author | Miller, A | |
dc.contributor.author | Shim, KG | |
dc.contributor.author | Molan, A | |
dc.contributor.author | Wetmore, C | |
dc.contributor.author | Selby, P | |
dc.contributor.author | Samson, A | |
dc.contributor.author | Harrington, K | |
dc.contributor.author | Pandha, H | |
dc.contributor.author | Melcher, A | |
dc.contributor.author | Pulido, JS | |
dc.contributor.author | Harris, R | |
dc.contributor.author | Evgin, L | |
dc.contributor.author | Vile, RG | |
dc.date.accessioned | 2020-04-02T15:35:21Z | |
dc.date.issued | 2020-02-07 | |
dc.identifier.citation | Nature communications, 2020, 11 (1), pp. 790 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3580 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-020-14568-7 | |
dc.description.abstract | APOBEC3B, an anti-viral cytidine deaminase which induces DNA mutations, has been implicated as a mediator of cancer evolution and therapeutic resistance. Mutational plasticity also drives generation of neoepitopes, which prime anti-tumor T cells. Here, we show that overexpression of APOBEC3B in tumors increases resistance to chemotherapy, but simultaneously heightens sensitivity to immune checkpoint blockade in a murine model of melanoma. However, in the vaccine setting, APOBEC3B-mediated mutations reproducibly generate heteroclitic neoepitopes in vaccine cells which activate de novo T cell responses. These cross react against parental, unmodified tumors and lead to a high rate of cures in both subcutaneous and intra-cranial tumor models. Heteroclitic Epitope Activated Therapy (HEAT) dispenses with the need to identify patient specific neoepitopes and tumor reactive T cells ex vivo. Thus, actively driving a high mutational load in tumor cell vaccines increases their immunogenicity to drive anti-tumor therapy in combination with immune checkpoint blockade. | |
dc.format | Electronic | |
dc.format.extent | 790 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Killer Cells, Natural | |
dc.subject | T-Lymphocytes | |
dc.subject | Cell Line, Tumor | |
dc.subject | Animals | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Humans | |
dc.subject | Melanoma | |
dc.subject | Melanoma, Experimental | |
dc.subject | Cytidine Deaminase | |
dc.subject | Cancer Vaccines | |
dc.subject | Minor Histocompatibility Antigens | |
dc.subject | Epitopes | |
dc.subject | Immunotherapy | |
dc.subject | Tumor Escape | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Mutation | |
dc.subject | Female | |
dc.title | APOBEC3B-mediated corruption of the tumor cell immunopeptidome induces heteroclitic neoepitopes for cancer immunotherapy. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-01-21 | |
rioxxterms.versionofrecord | 10.1038/s41467-020-14568-7 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-02-07 | |
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/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 | 11 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Targeted Therapy | |
icr.researchteam | Translational Immunotherapy | |
dc.contributor.icrauthor | Harrington, Kevin | |
dc.contributor.icrauthor | Melcher, Alan | |