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

Biochem Biophys Res Commun. 2019 Apr 9;511(3):711-717. doi: 10.1016/j.bbrc.2019.02.094. Epub 2019 Mar 1.


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.

Keywords: Cytotoxic T lymphocytes; Glypican-3; Immunotherapy; Induced pluripotent stem cell; Regenerative medicine; Tumor formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Glypicans / analysis
  • Glypicans / immunology*
  • HLA-A2 Antigen / immunology
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / immunology*
  • Mice, Inbred NOD
  • Mice, SCID
  • Models, Molecular
  • Neoplasms / immunology
  • T-Lymphocytes, Cytotoxic / immunology*


  • GPC3 protein, human
  • Glypicans
  • HLA-A2 Antigen