PMID- 25532027
OWN - NLM
STAT- MEDLINE
DCOM- 20150821
LR  - 20181202
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 46
IP  - 2
DP  - 2015 Feb
TI  - A peptide antigen derived from EGFR T790M is immunogenic in non‑small cell lung 
      cancer.
PG  - 497-504
LID - 10.3892/ijo.2014.2787 [doi]
AB  - 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-gamma (IFN-gamma) 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.
FAU - Ofuji, Kazuya
AU  - Ofuji K
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
FAU - Tada, Yoshitaka
AU  - Tada Y
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
FAU - Yoshikawa, Toshiaki
AU  - Yoshikawa T
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
FAU - Shimomura, Manami
AU  - Shimomura M
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
FAU - Yoshimura, Mayuko
AU  - Yoshimura M
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
FAU - Saito, Keigo
AU  - Saito K
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
FAU - Nakamoto, Yasunari
AU  - Nakamoto Y
AD  - Second Department of Internal Medicine, Faculty of Medical Sciences, University 
      of Fukui, Fukui, Japan.
FAU - Nakatsura, Tetsuya
AU  - Nakatsura T
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Chiba, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141201
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Peptides)
RN  - 0 (Quinazolines)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Carcinoma, Non-Small-Cell Lung/genetics/*immunology/*therapy
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Drug Resistance, Neoplasm/immunology
MH  - ErbB Receptors/genetics/*immunology
MH  - Erlotinib Hydrochloride
MH  - Gefitinib
MH  - HLA-A2 Antigen/immunology
MH  - Humans
MH  - *Immunotherapy
MH  - Mutation
MH  - Peptides/genetics/*immunology/therapeutic use
MH  - Quinazolines/therapeutic use
PMC - PMC4277252
EDAT- 2014/12/23 06:00
MHDA- 2015/08/22 06:00
PMCR- 2014/12/01
CRDT- 2014/12/23 06:00
PHST- 2014/08/29 00:00 [received]
PHST- 2014/10/09 00:00 [accepted]
PHST- 2014/12/23 06:00 [entrez]
PHST- 2014/12/23 06:00 [pubmed]
PHST- 2015/08/22 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - ijo-46-02-0497 [pii]
AID - 10.3892/ijo.2014.2787 [doi]
PST - ppublish
SO  - Int J Oncol. 2015 Feb;46(2):497-504. doi: 10.3892/ijo.2014.2787. Epub 2014 Dec 1.