PMID- 32391625
OWN - NLM
STAT- MEDLINE
DCOM- 20201207
LR  - 20220603
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 111
IP  - 8
DP  - 2020 Aug
TI  - Efficacy of immunotherapy targeting the neoantigen derived from epidermal growth 
      factor receptor T790M/C797S mutation in non-small cell lung cancer.
PG  - 2736-2746
LID - 10.1111/cas.14451 [doi]
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide. Epidermal 
      growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) often have good 
      clinical activity against non-small cell lung cancer (NSCLC) with activating EGFR 
      mutations. Osimertinib, which is a third-generation EGFR-TKI, has a clinical 
      effect even on NSCLC harboring the threonine to methionine change at codon 790 of 
      EGFR (EGFR T790M) mutation that causes TKI resistance. However, most NSCLC 
      patients develop acquired resistance to osimertinib within approximately 1 year, 
      and 40% of these patients have the EGFR T790M and cysteine to serine change at 
      codon 797 (C797S) mutations. Therefore, there is an urgent need for the 
      development of novel treatment strategies for NSCLC patients with the EGFR 
      T790M/C797S mutation. In this study, we identified the EGFR T790M/C797S 
      mutation-derived peptide (790-799) (MQLMPFGSLL) that binds the human leukocyte 
      antigen (HLA)-A*02:01, and successfully established EGFR 
      T790M/C797S-peptide-specific CTL clones from human PBMC of HLA-A2 healthy donors. 
      One established CTL clone demonstrated adequate cytotoxicity against T2 cells 
      pulsed with the EGFR T790M/C797S peptide. This CTL clone also had high reactivity 
      against cancer cells that expressed an endogenous EGFR T790M/C797S peptide using 
      an interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay. In addition, we 
      demonstrated using a mouse model that EGFR T790M/C797S peptide-specific CTL were 
      induced by EGFR T790M/C797S peptide vaccine in vivo. These findings suggest that 
      an immunotherapy targeting a neoantigen derived from EGFR T790M/C797S mutation 
      could be a useful novel therapeutic strategy for NSCLC patients with EGFR-TKI 
      resistance, especially those resistant to osimertinib.
CI  - (c) 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd 
      on behalf of Japanese Cancer Association.
FAU - Akazawa, Yu
AU  - Akazawa Y
AUID- ORCID: 0000-0002-8030-7373
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Japan.
AD  - Second Department of Internal Medicine, Faculty of Medical Sciences, University 
      of Fukui, Fukui, Japan.
FAU - Saito, Yuki
AU  - Saito Y
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Japan.
FAU - Yoshikawa, Toshiaki
AU  - Yoshikawa T
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Japan.
FAU - Saito, Keigo
AU  - Saito K
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Japan.
FAU - Nosaka, Kazuto
AU  - Nosaka K
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Japan.
AD  - Department of Obstetrics and Gynecology, Nagoya University Graduate School of 
      Medicine, Nagoya, Japan.
FAU - Shimomura, Manami
AU  - Shimomura M
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Japan.
FAU - Mizuno, Shoichi
AU  - Mizuno S
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, 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
AUID- ORCID: 0000-0003-3918-2385
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, Kashiwa, Japan.
LA  - eng
GR  - 25-7/National Cancer Center Research and Development Fund/
GR  - 28-A-8/National Cancer Center Research and Development Fund/
PT  - Journal Article
DEP - 20200618
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Acrylamides)
RN  - 0 (Aniline Compounds)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Vaccines, Subunit)
RN  - 3C06JJ0Z2O (osimertinib)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Acrylamides/pharmacology/therapeutic use
MH  - Aniline Compounds/pharmacology/therapeutic use
MH  - Animals
MH  - Antigens, Neoplasm/administration & dosage/genetics/immunology
MH  - Cancer Vaccines/*administration & dosage/genetics/immunology
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/immunology
MH  - Cell Line, Tumor
MH  - Drug Resistance, Neoplasm/genetics/immunology
MH  - Epitopes, T-Lymphocyte/genetics/immunology
MH  - ErbB Receptors/antagonists & inhibitors/genetics/immunology
MH  - HLA-A2 Antigen/genetics/immunology
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Lung Neoplasms/*drug therapy/genetics/immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Protein Kinase Inhibitors/pharmacology/therapeutic use
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Vaccines, Subunit/administration & dosage/genetics/immunology
PMC - PMC7419036
OTO - NOTNLM
OT  - C797S mutation
OT  - EGFR T790M
OT  - immunotherapy
OT  - neoantigen
OT  - non-small cell lung cancer
COIS- The authors declare no conflict of interest.
EDAT- 2020/05/12 06:00
MHDA- 2020/12/15 06:00
PMCR- 2020/08/01
CRDT- 2020/05/12 06:00
PHST- 2020/02/14 00:00 [received]
PHST- 2020/04/03 00:00 [revised]
PHST- 2020/04/06 00:00 [accepted]
PHST- 2020/05/12 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/05/12 06:00 [entrez]
PHST- 2020/08/01 00:00 [pmc-release]
AID - CAS14451 [pii]
AID - 10.1111/cas.14451 [doi]
PST - ppublish
SO  - Cancer Sci. 2020 Aug;111(8):2736-2746. doi: 10.1111/cas.14451. Epub 2020 Jun 18.