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

被引：71

作者：

Ando, Miki ^{[1
]}

Nishimura, Toshinobu ^{[1
,12
]}

Yamazaki, Satoshi ^{[1
]}

Yamaguchi, Tomoyuki ^{[1
]}

Kawana-Tachikawa, Ai ^{[2
,11
]}

Hayama, Tomonari ^{[1
]}

Nakauchi, Yusuke ^{[1
]}

Ando, Jun ^{[5
]}

Ota, Yasunori ^{[3
]}

Takahashi, Satoshi ^{[4
]}

Nishimura, Ken ^{[6
]}

Ohtaka, Manami ^{[7
]}

Nakanishi, Mahito ^{[7
]}

Miles, John J. ^{[8
]}

Burrows, Scott R. ^{[8
]}

Brenner, Malcolm K. ^{[9
,10
]}

Nakauchi, Hiromitsu ^{[1
,12
]}

机构：

[1] Univ Tokyo, Div Stem Cell Therapy, Ctr Stem Cell Biol & Regenerat Med, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan

[2] Univ Tokyo, Div Infect Dis, Adv Clin Res Ctr, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan

[3] Univ Tokyo, Dept Pathol, Res Hosp, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan

[4] Univ Tokyo, Div Mol Therapy, Adv Clin Res Ctr, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan

[5] Juntendo Univ, Dept Hematol, Sch Med, Bunkyo Ku, Tokyo 1138421, Japan

[6] Univ Tsukuba, Lab Gene Regulat, Fac Med, Tsukuba, Ibaraki 3058575, Japan

[7] Natl Inst Adv Ind Sci & Technol, Biotechnol Res Inst Drug Discovery, Tsukuba, Ibaraki 3058562, Japan

[8] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia

[9] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA

[10] Houston Methodist Hosp, Feigin Ctr, Houston, TX 77030 USA

[11] Natl Inst Infect Dis, AIDS Res Ctr, Shinjuku Ku, Tokyo 1628640, Japan

[12] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

来源：

STEM CELL REPORTS | 2015年 / 5卷 / 04期

基金：

日本科学技术振兴机构; 英国医学研究理事会;

关键词：

CASPASE-9 SAFETY SWITCH; SUICIDE-GENE; DONOR LYMPHOCYTES; IPS CELLS; GENERATION; APOPTOSIS; INHIBITION; EFFICIENT; ANTIBODY; EPITOPE;

D O I：

10.1016/j.stemcr.2015.07.011

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

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.

引用

页码：597 / 608

页数：12

共 48 条

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