A Safeguard System for Induced Pluripotent Stem Cell-Derived Rejuvenated T Cell Therapy

Stem Cell Reports
Miki AndoHiromitsu Nakauchi

Abstract

The discovery of induced pluripotent stem cells (iPSCs) has created promising new avenues for therapies in regenerative medicine. However, the tumorigenic potential of undifferentiated iPSCs is a major safety concern for clinical translation. To address this issue, we demonstrated the efficacy of suicide gene therapy by introducing inducible caspase-9 (iC9) into iPSCs. Activation of iC9 with a specific chemical inducer of dimerization (CID) initiates a caspase cascade that eliminates iPSCs and tumors originated from iPSCs. We introduced this iC9/CID safeguard system into a previously reported iPSC-derived, rejuvenated cytotoxic T lymphocyte (rejCTL) therapy model and confirmed that we can generate rejCTLs from iPSCs expressing high levels of iC9 without disturbing antigen-specific killing activity. iC9-expressing rejCTLs exert antitumor effects in vivo. The system efficiently and safely induces apoptosis in these rejCTLs. These results unite to suggest that the iC9/CID safeguard system is a promising tool for future iPSC-mediated approaches to clinical therapy.

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Citations

Nov 22, 2015·Seminars in Immunology·Peter KaragiannisShin Kaneko
Nov 9, 2016·Experimental Hematology·Miki Ando, Hiromitsu Nakauchi
Apr 27, 2016·World Journal of Stem Cells·Paola SpitalieriFederica Sangiuolo
Apr 9, 2020·International Journal of Molecular Sciences·Alexandra LipusNico Lachmann
Jul 15, 2020·Nature Biotechnology·Volker WiebkingMatthew H Porteus
Mar 2, 2017·Cellular and Molecular Life Sciences : CMLS·Ho-Chang JeongHyuk-Jin Cha
Aug 30, 2017·In Vitro Cellular & Developmental Biology. Animal·Saoko TachikawaKiyoshi Ohnuma
Jul 15, 2020·Stem Cells Translational Medicine·Zhong-Dong ShiAaron J Carman
Jun 28, 2019·Current Hematologic Malignancy Reports·Alexandros Nianias, Maria Themeli
Jun 14, 2019·Stem Cells International·Methichit Wattanapanitch
Jan 24, 2020·Molecular Therapy. Methods & Clinical Development·Seiji NaganoHiroshi Kawamoto
Apr 20, 2021·Molecular Therapy. Methods & Clinical Development·Yoshihiro IwamotoShin Kaneko
Aug 28, 2021·Frontiers in Endocrinology·Meghan Tahbaz, Eiji Yoshihara
Aug 14, 2021·Cancer Immunology Research·Midori IshiiMiki Ando
Oct 11, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sakiko HaradaNorio Komatsu
Oct 30, 2021·Frontiers in Genome Editing·Henriette Reventlow FrederiksenKristine K Freude
Oct 19, 2021·International Immunology·Hiroshi KawamotoSeiji Nagano

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Methods Mentioned

BETA
flow cytometry
xenograft

Software Mentioned

Prism
Xenogen Living Image
GraphPad
Excel
FlowJo

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