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

Marina Okada1, Yoshitaka Tada2, Tomohisa Seki1

  • 1Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-cu, Tokyo, 160-8582, Japan.

Biochemical and Biophysical Research Communications
|March 5, 2019
PubMed

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 lymphocytesGlypican-3ImmunotherapyInduced pluripotent stem cellRegenerative medicineTumor formation

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