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

Marina Okada, Yoshitaka Tada, Tomohisa Seki, Shugo Tohyama, Jun Fujita, Toshihiro Suzuki, Manami Shimomura, Kazuya Ofuji, Yoshikazu Kishino, Kazuaki Nakajima, Sho Tanosaki, Shota Someya, Hideaki Kanazawa, Satoru Senju, Tetsuya Nakatsura, Keiichi Fukuda

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Abstract

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.

Original languageEnglish
JournalBiochemical and Biophysical Research Communications
DOIs
Publication statusPublished - 2019 Jan 1

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Keywords

  • Cytotoxic T lymphocytes
  • Glypican-3
  • Immunotherapy
  • Induced pluripotent stem cell
  • Regenerative medicine
  • Tumor formation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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