Ex vivo expansion of natural killer cells with high cytotoxicity by K562 cells modified to co-express major histocompatibility complex class I chain-related protein A, 4-1BB ligand, and interleukin-15
Ex vivo expansion of natural killer cells with high cytotoxicity by K562 cells modified to co-express major histocompatibility complex class I chain-related protein A, 4-1BB ligand, and interleukin-15
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通过修饰共表达主要组织相容性复合物 I 类链相关蛋白 A、4-1BB 配体和白细胞介素 15 的 K562 细胞，体外扩增具有高细胞毒性的自然杀伤细胞
DOI：
10.1111/j.1399-0039.2010.01535.x
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发表时间：
2010-12-01
期刊：
影响因子：
--
通讯作者：
Ji, M.
中科院分区：
文献类型：
--
作者：
Gong, W.;Xiao, W.;Ji, M.
尤其是在肿瘤过继性免疫治疗中，预计会产生大量具有高功能的自然杀伤（NK）细胞。 K562 细胞经过基因改造，可共表达主要组织相容性复合物 I 类链相关蛋白 A (MICA)、4-1BB 配体和 IL-15，称为 K562-MICA-4-1BBL-IL-15。修饰后的K562细胞不仅促进NK细胞的活化、增殖和存活，而且增强NK细胞的细胞毒性。在长期培养测试中，K562-MICA-4-1BBL-IL-15细胞在24天的培养中刺激NK细胞平均扩增550倍，并从第1天占外周血单克隆淋巴细胞总数的14.8％增加到第24天的86.7％。扩增后普遍存在的NK细胞增强了杀伤靶标和产生干扰素γ（IFN-γ）的能力，并保持激活的高表达受体。结果表明，K562-MICA-4-1BBL-IL-15细胞将被开发用于体外扩增NK细胞，并可能对临床免疫治疗产生重要影响。
A large number of natural killer (NK) cells with high function are expected to generate especially in tumor adoptive immunotherapy. Here K562 cells were genetically modified to co-express major histocompatibility complex class I chain-related protein A (MICA), 4-1BB ligand, and IL-15, called K562-MICA-4-1BBL-IL-15. The modified K562 cells not only promoted activation, proliferation, and survival of NK cells, but also enhanced NK cell cytotoxicity. In long-term culture tests, K562-MICA-4-1BBL-IL-15 cells stimulated NK cell to expand mean 550 folds in 24-day culture and to cover from 14.8% of total peripheral blood monoclonal lymphocytes on day 1 to 86.7% on day 24. Prevalent NK cells after expansion enhanced the ability of killing targets and producing interferon gamma (IFN-gamma), and kept high expression of activating receptors. The results indicated that K562-MICA-4-1BBL-IL-15 cells would be developed for expansion of NK cells ex vivo and may have important implications for clinical immunotherapy.