Stem Cell Reports
Volume 5, Issue 4, 13 October 2015, Pages 597-608
Journal home page for Stem Cell Reports

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

https://doi.org/10.1016/j.stemcr.2015.07.011Get rights and content
Under a Creative Commons license
open access

Highlights

  • iPSC-derived rejuvenated CTLs are effective against EBV-induced tumors in vivo

  • Rejuvenated CTLs are implemented with an inducible caspase-9 (iC9)-based suicide system

  • Upon induction, the iC9 system efficiently leads to apoptosis in rejuvenated CTLs

  • The iC9-based system provides a safeguard for future iPSC-mediated cell therapy

Summary

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.

Cited by (0)

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).