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dc.contributor.authorYamada, Teppeien_US
dc.contributor.authorAzuma, Koichien_US
dc.contributor.authorMuta, Emien_US
dc.contributor.authorKim, Jintaeken_US
dc.contributor.authorSugawara, Shunichien_US
dc.contributor.authorZhang, Guang Lanen_US
dc.contributor.authorMatsueda, Satokoen_US
dc.contributor.authorKasama-Kawaguchi, Yurien_US
dc.contributor.authorYamashita, Yuichien_US
dc.contributor.authorYamashita, Takutoen_US
dc.contributor.authorNishio, Kazutoen_US
dc.contributor.authorItoh, Kyogoen_US
dc.contributor.authorHoshino, Tomoakien_US
dc.contributor.authorSasada, Tetsuroen_US
dc.coverage.spatialUnited Statesen_US
dc.date2013-09-19
dc.date.accessioned2017-10-24T18:11:35Z
dc.date.available2017-10-24T18:11:35Z
dc.date.issued2013
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/24223798
dc.identifier.citationTeppei Yamada, Koichi Azuma, Emi Muta, Jintaek Kim, Shunichi Sugawara, Guang Lan Zhang, Satoko Matsueda, Yuri Kasama-Kawaguchi, Yuichi Yamashita, Takuto Yamashita, Kazuto Nishio, Kyogo Itoh, Tomoaki Hoshino, Tetsuro Sasada. 2013. "EGFR T790M mutation as a possible target for immunotherapy; identification of HLA-A*0201-restricted T cell epitopes derived from the EGFR T790M mutation.." PLoS One, Volume 8, Issue 11, pp. e78389 -10 p.
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/2144/24324
dc.description.abstractTreatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, has achieved high clinical response rates in patients with non-small cell lung cancers (NSCLCs). However, over time, most tumors develop acquired resistance to EGFR-TKIs, which is associated with the secondary EGFR T790M resistance mutation in about half the cases. Currently there are no effective treatment options for patients with this resistance mutation. Here we identified two novel HLA-A*0201 (A2)-restricted T cell epitopes containing the mutated methionine residue of the EGFR T790M mutation, T790M-5 (MQLMPFGCLL) and T790M-7 (LIMQLMPFGCL), as potential targets for EGFR-TKI-resistant patients. When peripheral blood cells were repeatedly stimulated in vitro with these two peptides and assessed by antigen-specific IFN-γ secretion, T cell lines responsive to T790M-5 and T790M-7 were established in 5 of 6 (83%) and 3 of 6 (50%) healthy donors, respectively. Additionally, the T790M-5- and T790M-7-specific T cell lines displayed an MHC class I-restricted reactivity against NSCLC cell lines expressing both HLA-A2 and the T790M mutation. Interestingly, the NSCLC patients with antigen-specific T cell responses to these epitopes showed a significantly less frequency of EGFR-T790M mutation than those without them [1 of 7 (14%) vs 9 of 15 (60%); chi-squared test, p  =  0.0449], indicating the negative correlation between the immune responses to the EGFR-T790M-derived epitopes and the presence of EGFR-T790M mutation in NSCLC patients. This finding could possibly be explained by the hypothesis that immune responses to the mutated neo-antigens derived from T790M might prevent the emergence of tumor cell variants with the T790M resistance mutation in NSCLC patients during EGFR-TKI treatment. Together, our results suggest that the identified T cell epitopes might provide a novel immunotherapeutic approach for prevention and/or treatment of EGFR-TKI resistance with the secondary EGFR T790M resistance mutation in NSCLC patients.en_US
dc.format.extente78389 - 10 p.en_US
dc.languageeng
dc.language.isoen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofPLoS One
dc.subjectFemaleen_US
dc.subjectHumansen_US
dc.subjectImmunotherapyen_US
dc.subjectMaleen_US
dc.subjectMutationen_US
dc.subjectQuinazolinesen_US
dc.subjectMutationen_US
dc.subjectAgeden_US
dc.subjectScience & technologyen_US
dc.subjectMultidisciplinary sciencesen_US
dc.subjectGrowth-factor receptoren_US
dc.subjectTyrosine kinase inhibitorsen_US
dc.subjectTherapeutic cancer vaccinesen_US
dc.subjectLung canceren_US
dc.subjectAcquired resistanceen_US
dc.subjectClinical responseen_US
dc.subjectPeptide complexen_US
dc.subjectPoint mutationen_US
dc.subjectHigh-affinityen_US
dc.subjectGefitiniben_US
dc.subjectAmino acid sequenceen_US
dc.subjectAntineoplastic agentsen_US
dc.subjectCarcinoma, non-small-cell lungen_US
dc.subjectDrug resistance, neoplasmen_US
dc.subjectEpitopes, T-lymphocyteen_US
dc.subjectErlotinib hydrochlorideen_US
dc.subjectGene expression regulation, neoplasticen_US
dc.subjectHLA-A2 antigenen_US
dc.subjectLeukocytes, mononuclearen_US
dc.subjectLung neoplasmsen_US
dc.subjectLymphocyte activationen_US
dc.subjectMiddle ageden_US
dc.subjectMolecular sequence dataen_US
dc.subjectProtein kinase inhibitorsen_US
dc.subjectReceptor, epidermal growth factoren_US
dc.titleEGFR T790M mutation as a possible target for immunotherapy; identification of HLA-A*0201-restricted T cell epitopes derived from the EGFR T790M mutationen_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pone.0078389
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, Metropolitan Collegeen_US
pubs.publication-statusPublished onlineen_US
dc.identifier.orcid0000-0001-6010-490X (Zhang, Guang Lan)


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