• 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, and Hiromitsu Nakauchi.
• Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
• Stem Cell Reports. 2015 Oct 13; 5 (4): 597-608.

AbstractThe 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.Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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