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

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., and Nakauchi, Hiromitsu (2015) A safeguard system for induced pluripotent stem cell-derived rejuvenated T cell therapy. Stem Cell Reports, 5 (4). pp. 597-608.

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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.

Item ID: 44962
Item Type: Article (Research - C1)
ISSN: 2213-6711
Additional Information:

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

Funders: Japan Society for Promotion of Science (JSPS), Japan Science and Technology Agency (JSTA), Ministry of Health, Labour and Welfare (MHLW), California Institute of Regenerative Medicine (CIRM), Virginia and D.K. Ludwig Fund for Cancer Research (VDKLFCR), National Health and Medical Research Council of Australia (NHMRC)
Date Deposited: 03 Aug 2016 03:53
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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