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

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2015 Sep 1

PMID 26321144

Citations 39

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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