TY - JOUR
T1 - Selective elimination of undifferentiated human pluripotent stem cells using pluripotent state-specific immunogenic antigen Glypican-3
AU - Okada, Marina
AU - Tada, Yoshitaka
AU - Seki, Tomohisa
AU - Tohyama, Shugo
AU - Fujita, Jun
AU - Suzuki, Toshihiro
AU - Shimomura, Manami
AU - Ofuji, Kazuya
AU - Kishino, Yoshikazu
AU - Nakajima, Kazuaki
AU - Tanosaki, Sho
AU - Someya, Shota
AU - Kanazawa, Hideaki
AU - Senju, Satoru
AU - Nakatsura, Tetsuya
AU - Fukuda, Keiichi
N1 - Funding Information:
The authors thank Drs. Katsuya Tsuchihara and Sachiyo Mimaki for technical assistance with RNA sequencing (Division of Translational Research, National Cancer Center). The authors also thank Profs. Hideyuki Okano (Department of Physiology, Keio University) and Masaya Nakamura (Department of Orthopaedic Surgery, Keio University) for providing lentiviral vector (CSII-EF-dVenus-Luc2). This work was mainly supported by Research Project for Practical Application of Regenerative Medicine from the Japan Agency for Medical Research and Development (AMED) and partly supported by the National Cancer Center Research and Development Fund (25-A-7) and (28-A-8), as well as Health and Labor Science Research Grants for Clinical Research on Applying Health Technology and Research for Promotion of Cancer Control Programmes, Japan.
Funding Information:
The authors thank Drs. Katsuya Tsuchihara and Sachiyo Mimaki for technical assistance with RNA sequencing (Division of Translational Research, National Cancer Center). The authors also thank Profs. Hideyuki Okano (Department of Physiology, Keio University) and Masaya Nakamura (Department of Orthopaedic Surgery, Keio University) for providing lentiviral vector (CSII-EF-dVenus-Luc2). This work was mainly supported by Research Project for Practical Application of Regenerative Medicine from the Japan Agency for Medical Research and Development (AMED) and partly supported by the National Cancer Center Research and Development Fund ( 25-A-7 ) and ( 28-A-8 ), as well as Health and Labor Science Research Grants for Clinical Research on Applying Health Technology and Research for Promotion of Cancer Control Programmes, Japan.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/4/9
Y1 - 2019/4/9
N2 - 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.
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.
KW - Cytotoxic T lymphocytes
KW - Glypican-3
KW - Immunotherapy
KW - Induced pluripotent stem cell
KW - Regenerative medicine
KW - Tumor formation
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U2 - 10.1016/j.bbrc.2019.02.094
DO - 10.1016/j.bbrc.2019.02.094
M3 - Article
C2 - 30827508
AN - SCOPUS:85062148622
SN - 0006-291X
VL - 511
SP - 711
EP - 717
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -
