Expansion of NK cells from cord blood with antileukemic activity using GMP-compliant substances without feeder cells
Expansion of NK cells from cord blood with antileukemic activity using GMP-compliant substances without feeder cells
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DOI：
10.1038/leu.2011.345
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发表时间：
2012-05
期刊：
影响因子：
11.4
通讯作者：
J. Tanaka;J. Sugita;S. Shiratori;A. Shigematu;S. Asanuma;K. Fujimoto;M. Nishio;T. Kondo;M. Imamura
中科院分区：
文献类型：
--
作者：
J. Tanaka;J. Sugita;S. Shiratori;A. Shigematu;S. Asanuma;K. Fujimoto;M. Nishio;T. Kondo;M. Imamura
新生儿脐带血（CB）细胞已被证明含有高百分比的自然杀伤（NK）细胞，但NK细胞是不成熟的，具有低水平的细胞溶解活性。然而，已报道CB NK细胞中穿孔素和颗粒酶的表达水平高，并且已表明CB NK细胞在表型和功能上成熟。研究表明，CB是一种与骨髓或动员的外周血一样安全有效的干细胞来源。1，2此外，CB中有许多祖细胞群可以分化为NK细胞。因此，CB是扩增用于过继免疫治疗的NK细胞的有用来源，特别是针对表达低水平的人白细胞抗原I类分子的恶性细胞。静息CB NK细胞通过增加细胞溶解活性快速响应细胞因子刺激。同种异体NK细胞的连续转移是诱导移植物抗白血病（GVL）效应而不引起移植物抗宿主病（GVHD）的潜在免疫疗法。3在这项研究中，我们尝试使用符合良好生产规范（GMP）的物质，不使用饲养细胞，从具有抗白血病活性的CB中扩增NK细胞。我们使用他克莫司（FK506）和低分子
Neonatal cord blood (CB) cells have been demonstrated to contain a high percentage of natural killer (NK) cells, but the NK cells are immature, with a low level of cytolytic activity. However, expression levels of perforin and granzyme have been reported to be high in CB NK cells, and it has been suggested that CB NK cells are phenotypically and functionally mature. It has been suggested that CB is a source of stem cells that is as safe and effective as bone marrow or mobilized peripheral blood. 1, 2 Also, there are a number of progenitor cell populations in CB that can be differentiated to NK cells. Therefore, CB is a useful source to expand NK cells for adoptive immunotherapy, particularly against malignant cells that express a low level of human leukocyte antigen class I molecules. Resting CB NK cells rapidly respond to cytokine stimulation by increasing cytolytic activity. Adoptive transfer of allogeneic NK cells is a potential immunotherapy to induce a graft-versus-leukemia (GVL) effect, without causing a graft-versus-host disease (GVHD). 3 In this study, we tried to expand NK cells from CB with antileukemic activity using good manufacturing practice (GMP)-compliant substances without feeder cells. We used tacrolimus (FK506) and low molecular