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 - 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.
UR - https://www.scopus.com/pages/publications/85062148622
UR - https://www.scopus.com/inward/citedby.url?scp=85062148622&partnerID=8YFLogxK
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 -
