Generation and application of human induced-stem cell memory T cells for adoptive immunotherapy.
Generation and application of human induced-stem cell memory T cells for adoptive immunotherapy.
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DOI：
10.1111/cas.13648
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发表时间：
2018-07
期刊：
影响因子：
5.7
通讯作者：
Yoshimura A
中科院分区：
文献类型：
--
作者：
Kondo T;Imura Y;Chikuma S;Hibino S;Omata-Mise S;Ando M;Akanuma T;Iizuka M;Sakai R;Morita R;Yoshimura A
过继性T细胞治疗是一种有效的肿瘤免疫治疗策略。然而，输注的T细胞经常功能衰竭，因此移植到患者体内后预后较差。肿瘤抗原特异性干细胞记忆T （TSCM）细胞的过继转移有望克服这一缺点，因为TSCM细胞与naïve T细胞接近，但也具有高增殖性，长寿命，并在抗原刺激下产生大量效应T细胞。我们之前报道过激活的效应T细胞可以通过与表达Notch配体δ样1 （OP9 - hDLL1）的OP9细胞共培养转化为TSCM样细胞（iTSCM）。在这里，我们展示了人类CD8+ iTSCM细胞生成的方法学参数及其在过继性癌症免疫治疗中的应用。无论是抗CD3/CD28抗体还是抗原提呈细胞的刺激，中枢记忆型T细胞比效应记忆T细胞更有效地诱导人iTSCM细胞。在与OP9‐hDLL1细胞共培养的诱导阶段，白细胞介素（IL）‐7和IL‐15（但不包括IL‐2或IL‐21）可以有效地生成iTSCM细胞。Epstein-Barr病毒特异性iTSCM细胞在人源化Epstein-Barr病毒转化的肿瘤模型小鼠中显示出比常规激活的T细胞更强的抗肿瘤潜能。因此，iTSCM的过继T细胞治疗为癌症免疫治疗提供了一种很有前景的治疗策略。
Adoptive T‐cell therapy is an effective strategy for cancer immunotherapy. However, infused T cells frequently become functionally exhausted, and consequently offer a poor prognosis after transplantation into patients. Adoptive transfer of tumor antigen‐specific stem cell memory T (TSCM) cells is expected to overcome this shortcoming as TSCM cells are close to naïve T cells, but are also highly proliferative, long‐lived, and produce a large number of effector T cells in response to antigen stimulation. We previously reported that activated effector T cells can be converted into TSCM‐like cells (iTSCM) by coculturing with OP9 cells expressing Notch ligand, Delta‐like 1 (OP9‐hDLL1). Here we show the methodological parameters of human CD8+ iTSCM cell generation and their application to adoptive cancer immunotherapy. Regardless of the stimulation by anti‐CD3/CD28 antibodies or by antigen‐presenting cells, human iTSCM cells were more efficiently induced from central memory type T cells than from effector memory T cells. During the induction phase by coculture with OP9‐hDLL1 cells, interleukin (IL)‐7 and IL‐15 (but not IL‐2 or IL‐21) could efficiently generate iTSCM cells. Epstein–Barr virus‐specific iTSCM cells showed much stronger antitumor potentials than conventionally activated T cells in humanized Epstein–Barr virus transformed‐tumor model mice. Thus, adoptive T‐cell therapy with iTSCM offers a promising therapeutic strategy for cancer immunotherapy.
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DOI：
10.1038/nrc3322
发表时间：
2012-10
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Gattinoni L;Klebanoff CA;Restifo NP
通讯作者：
Restifo NP
影响因子：
82.9
作者：
Gattinoni L;Speiser DE;Lichterfeld M;Bonini C
通讯作者：
Bonini C
影响因子：
82.9
作者：
Gattinoni L;Lugli E;Ji Y;Pos Z;Paulos CM;Quigley MF;Almeida JR;Gostick E;Yu Z;Carpenito C;Wang E;Douek DC;Price DA;June CH;Marincola FM;Roederer M;Restifo NP
通讯作者：
Restifo NP
DOI：
10.1073/pnas.1610544113
发表时间：
2016-11-29
影响因子：
11.1
作者：
Hurton, Lenka V.;Singh, Harjeet;Cooper, Laurence J. N.
通讯作者：
Cooper, Laurence J. N.
DOI：
10.1038/nrc.2016.97
发表时间：
2016-08-23
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Fesnak AD;June CH;Levine BL
通讯作者：
Levine BL