Selective elimination of undifferentiated human pluripotent stem cells using pluripotent state-specific immunogenic antigen Glypican-3

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 immuno...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2019-04, Vol.511 (3), p.711-717
Main Authors: Okada, Marina, Tada, Yoshitaka, Seki, Tomohisa, Tohyama, Shugo, Fujita, Jun, Suzuki, Toshihiro, Shimomura, Manami, Ofuji, Kazuya, Kishino, Yoshikazu, Nakajima, Kazuaki, Tanosaki, Sho, Someya, Shota, Kanazawa, Hideaki, Senju, Satoru, Nakatsura, Tetsuya, Fukuda, Keiichi
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation
Cell Line
Cytotoxic T lymphocytes
Glypican-3
Glypicans - analysis
Glypicans - immunology
HLA-A2 Antigen - immunology
Humans
Immunotherapy
Induced pluripotent stem cell
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - immunology
Mice, Inbred NOD
Mice, SCID
Models, Molecular
Neoplasms - immunology
Regenerative medicine
T-Lymphocytes, Cytotoxic - immunology
Tumor formation
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Summary: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. •GPC3 is specifically expressed in hiPSCs.•GPC3-specific CTLs selectively remove undifferentiated hiPSCs in vitro.•GPC3-specific CTLs inhibit tumor formation in vivo.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2019.02.094