Cell子刊：iPSCs新突破，为癌症免疫疗法装上“安保系统”（附原文）

ghrthrt05

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$ M. Z6 i3 O1 M! d9 L1 _6 c% l, `9 e来源：生物探索
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; O4 ]8 S( w$ V9 _1 e" fHiromitsu Nakauchi教授
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8月27日，发表在《Stem Cell Reports》杂志上的一项研究中，日本东京大学的科学家们发现，利用诱导性多功能干细胞（Induced Pluripotent Stem cells，iPSCs）技术“再生”人类免疫T细胞能够有效减小小鼠体内肿瘤的体积。这一突破将加速T细胞免疫疗法的临床应用研究。
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2013年，东京大学医学科学研究所干细胞疗法分部Hiromitsu Nakauchi教授的研究小组成功开发了一种从iPSCs 恢复活力的“杀手”T细胞。然而，在这项技术在临床中安全使用之前，开发能够控制iPSCs以免它们癌变或产生其它副作用的技术至关重要。4 ?& s2 [' [: b6 w0 }
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1 u% a. E4 b, N2 r3 |在这项研究中，同一个研究小组的实验证明，iPSC-derived T-cells在小鼠体内实验和体外实验中都能够降低肿瘤的大小。此次，他们引入了一种叫iCaspase-9的基因到iPSCs中，该基因可诱导细胞自杀。$ S  M5 r5 S5 ]

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# ]/ n* a; a# f7 D7 r+ a; [实验中，研究者首先将病毒感染造成的人类癌变细胞移植到小白鼠体内，然后利用iPSCs培育出“杀手”T细胞，再回输到小鼠体内。结果显示，免疫细胞充分发挥作用，使癌细胞缩小到了原来的二十分之一左右。
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此外，研究小组证实，通过给予一种能够诱导细胞死亡的药物到iPSC-derived T-cells中能够在小鼠体内将这些T细胞消除。此外，研究还证明，如果在治疗中出现了副作用，通过以上途径也可能消除iPSC-derived T-cells。
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/ E& N# r0 y' R$ M这项研究提供了可以控制T细胞疗法中任何可能发生的副作用的方法，大大提高了实现安全的、有效的T细胞疗法的可能性。谈到这项最新的研究，Nakauchi教授说：“这项安全机制也可以用到其它iPSC衍生疗法中。”5 Y: m, Q- l9 ~9 r) l) I
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A safeguard system for iPSC-derived T-cell therapy4 c7 K9 ~5 g: X: y, F
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东京大学该实验室的网页：3 K4 `  k. s/ V3 H8 M8 v/ w, u
http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/a-safeguard-system-for-ipsc-derived-t-cell-therapy.html
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Researchers at the University of Tokyo showed that human immune T-cells rejuvenated using iPS cell techniques effectively reduced the size of tumors in mice, enhancing the safety of iPSC-derived T-cell therapy for eradicating target viruses by including a suicide gene in iPSC-derived T-cells that can be pharmaceutically triggered. This finding will accelerate research towards realizing clinical applications of this therapy.
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In 2013, Professor Hiromitsu Nakauchi’s research group at the University of Tokyo Institute of Medical Science’s Division of Stem Cell Therapy successfully developed a technique to produce killer T-cells, a type of immune cell, in a rejuvenated state from iPS cells. However, before this technique could be used safely in clinical settings, it was necessary to develop techniques to control the iPS cells in case they became cancerous or produced other side effects.2 P8 \9 r8 c" u, Y, R

8 s$ w! T1 n2 D# qThis time, the same group has experimentally demonstrated that rejuvenated killer T-cells effectively reduce tumor size both in mice and in vitro (in the test tube). In addition, they introduced a gene, iCaspase-9, into the iPS cells from which they then produced the rejuvenated killer T-cells. iCaspase-9 induces cell suicide. Compared to ordinary T-cells, these iPSC-derived T-cells were more effective at reducing the size of a tumor implanted into a mouse, and also extended the survival time of the mouse. Further, the research group confirmed that by administering a specific drug that induced cell death in the iPSC-derived T-cells it was possible to erase these T-cells in mice and demonstrating that if side effects were to appear in therapeutic use, it would be possible to eradicate the iPSC-derived T-cells.
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1 N* I, C6 w6 W1 {* F8 y; jThis research provides a means of completely controlling any side effects that might occur as a result of T-cell therapy, greatly advancing the possibility of safe and effective T-cell therapies. Speaking of his group’s latest research, Professor Nakauchi says “This safety mechanism can also be applied to other iPSC-derived therapies.”8 p# {" U% V" y