Characterization of stem cell factor gene-modified human natural killer cell line, NK-92 cells: implication in NK cell-based adoptive cellular immunotherapy.
Characterization of stem cell factor gene-modified human natural killer cell line, NK-92 cells: implication in NK cell-based adoptive cellular immunotherapy.
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DOI：
10.3892/or.11.5.1097
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发表时间：
2004-05
期刊：
影响因子：
4.2
通讯作者：
Jian Zhang;R. Sun;Haiming Wei;Jianhua Zhang;Z. Tian
中科院分区：
文献类型：
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作者：
Jian Zhang;R. Sun;Haiming Wei;Jianhua Zhang;Z. Tian
NK-92细胞在体内和体外都对多种恶性靶标有效。干细胞因子（Stem cell factor， SCF）是影响NK细胞发育的重要早期细胞因子。SCF基因修饰NK-92细胞的特性及其临床意义有待进一步研究。将SCF cDNA插入pcDNA3真核表达载体，将重组载体pcDNA3-SCF转染NK-92细胞。克隆了SCF基因修饰的NK-92细胞（NK92-SCF），并对细胞因子基因表达、增殖潜能、细胞毒功能和表面表型进行了表征。NK92-SCF细胞在培养上清液中持续产生高水平的SCF，使细胞在IL-2或IL-15刺激下增殖速度明显加快，长期培养的细胞累积数量明显增加。NK92-SCF细胞比其亲本NK-92细胞对多种靶肿瘤细胞表现出更强的细胞毒性，这与细胞毒性效应分子如穿孔素和Fas配体的表达增加有关。NK92-SCF细胞异质性增强；CD56（高）和CD56（低）亚群的出现，至少在一定程度上解释了NK92-SCF细胞的增殖和细胞毒性潜力的增加。SCF基因修饰的NK-92细胞（NK92-SCF细胞）比其亲本细胞更有希望用于过继细胞免疫治疗。
NK-92 cells are effective against a broad range of malignant targets both in vitro and in vivo. Stem cell factor (SCF) is an important early acting cytokine for NK cell development. The characterization and implication in clinic of SCF gene-modified NK-92 cells need to be investigated. SCF cDNA was inserted into pcDNA3 eukaryotic expression vector and the recombinant vector (pcDNA3-SCF) was transfected into NK-92 cells. The SCF gene-modified NK-92 cells (NK92-SCF) were cloned and characterized by cytokine gene expression, proliferation potential, cytotoxic function and surface phenotype. NK92-SCF cells continuously produced a high level of SCF in culture supernatant, which made the cells proliferate significantly more rapidly in response to IL-2 or IL-15 stimulation, the cumulative amount of cells in long-term culture was significantly higher. NK92-SCF cells exerted stronger cytotoxicity against a broad range of target tumor cells than their parent NK-92 cells, which was correlated to the increased expression of cytotoxic effector molecules such as perforin and Fas ligand. NK92-SCF cells became more heterogeneous; the CD56(High) and CD56(Low) subsets appeared, which may, at least partly, explain the increased proliferating and cytotoxic potential of NK92-SCF cells. SCF gene-modified NK-92 cells (NK92-SCF cells) are more promising than their parent cells for adoptive cellular immunotherapy.