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

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

来源：Stem Cell Reports, 2015, 5(4): 597-608.

DOI：10.1016/j.stemcr.2015.07.011

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.

• 出版日期2015-10-13
• 单位河北医科大学