Expansion and activation of natural killer cells for cancer immunotherapy.
Expansion and activation of natural killer cells for cancer immunotherapy.
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DOI：
10.3343/kjlm.2009.29.2.89
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
Campana D
中科院分区：
文献类型：
--
作者：
Cho D;Campana D
自然杀伤（NK）细胞可以杀死广泛的癌细胞，是一种有前途的癌症细胞治疗工具。NK细胞的细胞毒性受刺激和抑制信号之间的平衡调节。已知白细胞介素-2增加NK细胞的细胞毒性。虽然已经研究了许多细胞因子以诱导持久的NK细胞扩增，但大多数报告表明效果相当温和，并且需要额外的刺激。我们发现，与K562骨髓白血病细胞系（经过基因修饰以表达膜结合形式的白细胞介素-15和共刺激分子4-1BB的配体）接触，可诱导外周血NK细胞的剧烈扩增。基于这些发现，我们开发了一种用于大规模临床级NK细胞扩增的方法。这种方法目前用于扩增同种异体NK细胞，用于白血病和实体瘤患者的输注。我们在这里总结了从人外周血单核细胞中扩增和激活NK细胞的方法，以及在现行药品生产质量管理规范（cGMP）条件下生产用于免疫治疗的NK细胞的临床规模方法。
Natural killer (NK) cells can kill a wide range of cancer cells and are a promising tool for cell therapy of cancer. NK cells cytotoxicity is regulated by a balance between stimulatory and inhibitory signals. Interleukin-2 is known to increase NK cell cytotoxicity. Although many cytokines have been studied in efforts to induce durable NK cell expansions, most reports indicate a rather modest effect and the requirement for additional stimuli. We found that contact with the K562 myeloid leukemia cell line, genetically modified to express a membrane-bound form of interleukin-15 and the ligand for the costimulatory molecule 4-1BB, induced vigorous expansion of NK cells from peripheral blood. Based on these findings, we developed a method for large-scale clinical-grade expansion of NK cells. This method is currently used to expand allogeneic NK cells for infusion in patients with leukemia and solid tumors. We here summarize methods for expansion and activation of NK cells from human peripheral blood mononuclear cells as well as clinical-scale methods to produce NK cells for immunotherapy under Current Good Manufacturing Practices (cGMP) conditions.
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