Regeneration of tumor antigen-specific CTLs utilizing iPS technology

Regeneration of tumor antigen-specific CTLs utilizing iPS technology
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利用 iPS 技术再生肿瘤抗原特异性 CTL

DOI:
10.11406/rinketsu.57.1066
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发表时间:
2016
期刊:
Rinsho Ketsueki
影响因子:
--
通讯作者:
et al.
et al.
中科院分区:
--
文献类型:
--
作者:
Kataoka K;Shiraishi Y;Takeda Y;Sakata S;Matsumoto M;Suzuki H;Yoshiato T;Yoshida K;Sanada M. Itonaga H;Imaizumi Y;Totoki Y;Munakata W;Nakamura H;Hama N;Shide K;Kubuki Y;Hidaka T;Kameda T;Masuda K;et al.

文献摘要

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肿瘤免疫治疗,特别是肿瘤抗原特异性T细胞治疗,目前备受关注。然而,一个关键问题仍然有待解决;难以有效地扩增肿瘤抗原特异性T细胞。为了解决这个问题,我们现在正在利用iPS细胞技术。当从肿瘤抗原特异性T细胞建立iPS细胞时,预期从这些iPS细胞再生的T细胞表达与原始T细胞相同的TCR。根据这一概念,我们成功地再生了肿瘤抗原特异性细胞毒性T细胞。再生的T细胞表现出与原始细胞相当的TCR特异性杀伤活性,并且能够以抗原特异性方式杀伤白血病细胞。目前,我们正在努力将这种方法应用于临床。在未来,我们打算建立一个同种异体输血系统,其中来自广泛的HLA单倍型纯合供体的各种肿瘤抗原特异性T-iPS细胞将被排队作为“T-iPS细胞库”,目的是使现成的肿瘤免疫治疗成为现实。
Tumor immunotherapy, especially tumor antigen specific T cell therapy, is currently attracting attention. However, a critical issue still awaits resolution; it is difficult to efficiently expand tumor antigen-specific T cells. To solve this problem, we are now utilizing iPS cell technology. When iPS cells are established from tumor antigen specific T cells, T cells regenerated from these iPS cells are expected to express the same TCRs as the original T cells. In line with this concept, we succeeded in regenerating tumor antigen specific cytotoxic T cells. The regenerated T cells exhibited TCR specific killing activity comparable to that of the original cells, and were able to kill leukemia cells in an antigen-specific manner. We are currently endeavoring to apply this method clinically. In the future, we intend to establish an allogeneic transfusion system, in which various tumor antigen specific T-iPS cells from a wide range of HLA haplotype homozygous donors will be lined up as a" T-iPS cell bank", with the aim of making off-the-shelf tumor immunotherapy a reality.