PMID- 30827508
OWN - NLM
STAT- MEDLINE
DCOM- 20200121
LR  - 20200121
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 511
IP  - 3
DP  - 2019 Apr 9
TI  - Selective elimination of undifferentiated human pluripotent stem cells using 
      pluripotent state-specific immunogenic antigen Glypican-3.
PG  - 711-717
LID - S0006-291X(19)30285-2 [pii]
LID - 10.1016/j.bbrc.2019.02.094 [doi]
AB  - Immunogenicity of immature pluripotent stem cells is a topic of intense debate. 
      Immunogenic antigens, which are specific in pluripotent states, have not been 
      described previously. In this study, we identified glypican-3 (GPC3), a known 
      carcinoembryonic antigen, as a pluripotent state-specific immunogenic antigen. 
      Additionally, we validated the applicability of human leukocyte antigen 
      (HLA)-class I-restricted GPC3-reactive cytotoxic T lymphocytes (CTLs) in the 
      removal of undifferentiated pluripotent stem cells (PSCs) from human induced 
      pluripotent stem cell (hiPSC)-derivatives. HiPSCs uniquely express GPC3 in 
      pluripotent states and were rejected by GPC3-reactive CTLs, which were sensitized 
      with HLA-class I-restricted GPC3 peptides. Furthermore, GPC3-reactive CTLs 
      selectively removed undifferentiated PSCs from hiPSC-derivatives in vitro and 
      inhibited tumor formation in vivo. Our results demonstrate that GPC3 works as a 
      pluripotent state-specific immunogenic antigen in hiPSCs and is applicable to 
      regenerative medicine as a method of removing undifferentiated PSCs, which are 
      the main cause of tumor formation.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Okada, Marina
AU  - Okada M
AD  - Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi 
      Shinjuku-cu, Tokyo, 160-8582, Japan.
FAU - Tada, Yoshitaka
AU  - Tada Y
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, 
      Japan.
FAU - Seki, Tomohisa
AU  - Seki T
AD  - Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi 
      Shinjuku-cu, Tokyo, 160-8582, Japan.
FAU - Tohyama, Shugo
AU  - Tohyama S
AD  - Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi 
      Shinjuku-cu, Tokyo, 160-8582, Japan; Department of Organ Fabrication, Keio 
      University School of Medicine, 35 Shinanomachi Shinjuku-cu, Tokyo, 160-8582, 
      Japan.
FAU - Fujita, Jun
AU  - Fujita J
AD  - Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi 
      Shinjuku-cu, Tokyo, 160-8582, Japan.
FAU - Suzuki, Toshihiro
AU  - Suzuki T
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, 
      Japan.
FAU - Shimomura, Manami
AU  - Shimomura M
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, 
      Japan.
FAU - Ofuji, Kazuya
AU  - Ofuji K
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, 
      Japan.
FAU - Kishino, Yoshikazu
AU  - Kishino Y
AD  - Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi 
      Shinjuku-cu, Tokyo, 160-8582, Japan.
FAU - Nakajima, Kazuaki
AU  - Nakajima K
AD  - Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi 
      Shinjuku-cu, Tokyo, 160-8582, Japan.
FAU - Tanosaki, Sho
AU  - Tanosaki S
AD  - Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi 
      Shinjuku-cu, Tokyo, 160-8582, Japan.
FAU - Someya, Shota
AU  - Someya S
AD  - Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi 
      Shinjuku-cu, Tokyo, 160-8582, Japan.
FAU - Kanazawa, Hideaki
AU  - Kanazawa H
AD  - Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi 
      Shinjuku-cu, Tokyo, 160-8582, Japan.
FAU - Senju, Satoru
AU  - Senju S
AD  - Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto 
      University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
FAU - Nakatsura, Tetsuya
AU  - Nakatsura T
AD  - Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical 
      Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, 
      Japan. Electronic address: tnakatsu@east.ncc.go.jp.
FAU - Fukuda, Keiichi
AU  - Fukuda K
AD  - Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi 
      Shinjuku-cu, Tokyo, 160-8582, Japan. Electronic address: kfukuda@a2.keio.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190301
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (GPC3 protein, human)
RN  - 0 (Glypicans)
RN  - 0 (HLA-A2 Antigen)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Line
MH  - Glypicans/analysis/*immunology
MH  - HLA-A2 Antigen/immunology
MH  - Humans
MH  - Induced Pluripotent Stem Cells/cytology/*immunology
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Models, Molecular
MH  - Neoplasms/immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
OTO - NOTNLM
OT  - Cytotoxic T lymphocytes
OT  - Glypican-3
OT  - Immunotherapy
OT  - Induced pluripotent stem cell
OT  - Regenerative medicine
OT  - Tumor formation
EDAT- 2019/03/05 06:00
MHDA- 2020/01/22 06:00
CRDT- 2019/03/05 06:00
PHST- 2019/02/12 00:00 [received]
PHST- 2019/02/16 00:00 [accepted]
PHST- 2019/03/05 06:00 [pubmed]
PHST- 2020/01/22 06:00 [medline]
PHST- 2019/03/05 06:00 [entrez]
AID - S0006-291X(19)30285-2 [pii]
AID - 10.1016/j.bbrc.2019.02.094 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Apr 9;511(3):711-717. doi: 
      10.1016/j.bbrc.2019.02.094. Epub 2019 Mar 1.