Ex vivo generation of highly purified and activated natural killer cells from human peripheral blood.
Ex vivo generation of highly purified and activated natural killer cells from human peripheral blood.
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从人外周血中离体产生高度纯化和活化的自然杀伤细胞。
DOI：
10.1089/hgtb.2012.183
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Yonemitsu Y.
中科院分区：
文献类型：
--
作者：
Saito S;Harada Y;Morodomi Y;Onimaru M;Yoshida K;Kyuragi R;Matsubara H;Yonemitsu Y.
使用自然杀伤（NK）细胞的连续免疫疗法已经成为难治性恶性肿瘤的有希望的治疗;然而，关于效应细胞的短缺和有限的抗癌效力，仍然存在许多困难。我们在此建立了一种简单的无饲养层的方法，从人外周血来源的单核细胞（PBMC）中产生纯化的（>90%）和高度活化的NK细胞。在几个参数中，我们发现CD 3耗竭、高剂量白细胞介素（IL）-2和使用特定培养基足以从PBMC中获得高度纯化、扩增（约200倍）和活化的CD 3 −/CD 56 +NK细胞，我们将其命名为Zenithal-NK（Z-NK）细胞。几乎所有的Z-NK细胞都表达淋巴细胞活化的标志物CD 69，并显示出活化受体的显著高表达（即，NKG 2D）、干扰素-γ、穿孔素和颗粒酶B。重要的是，在效靶比为1：1的情况下，仅反应2小时就足以杀死几乎所有的K562细胞，并且在荷瘤小鼠体内也复制了抗肿瘤活性。细胞溶解是特定的各种肿瘤细胞，但不为正常细胞，不论MHC I类表达。这些发现有力地表明，Z-NK细胞是纯化的、扩增的和接近完全活化的人NK细胞，并且值得在临床环境中进一步研究。
Adoptive immunotherapy using natural killer (NK) cells has been a promising treatment for intractable malignancies; however, there remain a number of difficulties with respect to the shortage and limited anticancer potency of the effector cells. We here established a simple feeder-free method to generate purified (>90%) and highly activated NK cells from human peripheral blood-derived mononuclear cells (PBMCs). Among the several parameters, we found that CD3 depletion, high-dose interleukin (IL)-2, and use of a specific culture medium were sufficient to obtain highly purified, expanded (∼200-fold) and activated CD3−/CD56+NK cells from PBMCs, which we designated zenithal-NK (Z-NK) cells. Almost all Z-NK cells expressed the lymphocyte-activated marker CD69 and showed dramatically high expression of activation receptors (i.e., NKG2D), interferon-γ, perforin, and granzyme B. Importantly, only 2 hours of reaction at an effector/target ratio of 1:1 was sufficient to kill almost all K562 cells, and the antitumor activity was also replicated in tumor-bearing micein vivo. Cytolysis was specific for various tumor cells, but not for normal cells, irrespective of MHC class I expression. These findings strongly indicate that Z-NK cells are purified, expanded, and near-fully activated human NK cells and warrant further investigation in a clinical setting.
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DOI：
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发表时间：
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期刊：
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影响因子：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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