A safeguard system for induced pluripotent stem cell-derived rejuvenated T cell therapy

Miki Ando, Toshinobu Nishimura, Satoshi Yamazaki, Tomoyuki Yamaguchi, Ai Kawana-Tachikawa, Tomonari Hayama, Yusuke Nakauchi, Jun Ando, Yasunori Ota, Satoshi Takahashi, Ken Nishimura, Manami Ohtaka, Mahito Nakanishi, John J. Miles, Scott R. Burrows, Malcolm K. Brenner, Hiromitsu Nakauchi

Research output: Contribution to journalArticle

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)597-608
Number of pages12
JournalStem Cell Reports
Volume5
Issue number4
DOIs
StatePublished - Oct 13 2015

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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