title: A peptide antigen derived from EGFR T790M is immunogenic in non‑small cell lung cancer.
abstract: Lung cancer is the leading cause of cancer‑related deaths worldwide. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, have demonstrated marked clinical activity against non-small cell lung cancer (NSCLC) harboring activating epidermal growth factor receptor (EGFR) mutations. However, in most cases, patients develop acquired resistance to EGFR‑TKI therapy. The threonine to methionine change at codon 790 of EGFR (EGFR T790M) mutation is the most common acquired resistance mutation, and is present in ~50% cases of TKI resistance. New treatment strategies for NSCLC patients harboring the EGFR T790M mutation are required. We evaluated the immunogenicity of an antigen derived from EGFR with the T790M mutation. Using BIMAS we selected several EGFR T790M‑derived peptides bound to human leukocyte antigen (HLA)-A*02:01. T790M-A peptide (789-797) (IMQLMPFGC)-specific cytotoxic T lymphocytes (CTLs) were induced from peripheral blood mononuclear cells (PBMCs) of HLA-A2+ healthy donors. An established T790M-A-specific CTL line showed reactivity against the NCSLC cell line, H1975-A2 (HLA-A2+, T790M+), but not H1975 (HLA-A2-, T790M+), and the corresponding wild-type peptide (ITQLMPFGC)-pulsed T2 cells using an interferon-γ (IFN-γ) enzyme-linked immuno spot (ELISPOT) assay. This CTL line also demonstrated peptide-specific cytotoxicity against H1975-A2 cells. This finding suggests that the EGFR T790M mutation-derived antigen could be a new target for cancer immunotherapy.
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ofuji
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Shimomura
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Saito
authors.affiliation: Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Nakamoto
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000276:immunology; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D009154:Mutation; D010455:Peptides / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use
chemical_list: D015789:HLA-A2 Antigen; D010455:Peptides; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib