dc.contributor.author
Nyambura, Lydon Wainaina
dc.contributor.author
Muñoz, Alejandro Azorin
dc.contributor.author
Coutre, Philipp le
dc.contributor.author
Walden, Peter
dc.date.accessioned
2019-10-21T14:23:07Z
dc.date.available
2019-10-21T14:23:07Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/25767
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-25528
dc.description.abstract
Leukemia-associated antigens (LAAs) and HLA-I epitopes published previously have shown promise in inducing leukemia-specific T cell responses. However, the clinical responses are limited, and clinical effectiveness is yet to be achieved. Limitations, among others, being the LAAs themselves, the indirect approach to HLA-I epitope identification by reverse immunology, and the use of single or few LAAs and HLA-I epitopes, which limits the spectrum of inducible tumor-specific T cells. Use of a direct approach to identify naturally processed and presented HLA-I epitopes from LAAs, and higher numbers of antigens for T cell-mediated immunotherapy for leukemia may enhance clinical responses and broaden clinical effectiveness. In a prior study we used immunoaffinity purification of HLA-I peptide complexes from the differentiated myeloid tumor cell lines MUTZ3 and THP1 coupled to high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). From this we identified in the current study seven new HLA-I epitopes and the corresponding LAAs for myeloid leukemia. In comparison, the myeloid HLA-I epitopes reported here were generally stronger HLA-binders that induce stronger T cell responses than those previously published, and their source LAAs had higher immunogenicity, higher expression levels in myeloid tumors cells compared to normal hemopoietin and other major normal tissues, and more protein interaction partners, and they are targeted by CD8 T cells in CML patients. This study analyses and compares the LAAs and HLA-I epitopes based on various immunotherapeutic targets selection criteria, and highlights new targets for T cell-mediated immunotherapy for leukemia.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
immunotherapy
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
HLA class I-restricted T cell epitopes isolated and identified from myeloid leukemia cells
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
14029
dcterms.bibliographicCitation.doi
10.1038/s41598-019-50341-7
dcterms.bibliographicCitation.journaltitle
Scientific Reports
dcterms.bibliographicCitation.originalpublishername
Nature Publishing Group
dcterms.bibliographicCitation.volume
9
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
31575892
dcterms.isPartOf.eissn
2045-2322