白细胞介素12
细胞毒性T细胞
淋巴因子激活杀伤细胞
外周血单个核细胞
自然杀伤细胞
分子生物学
NK-92
白细胞介素2
生物
白细胞介素15
白细胞介素21
Janus激酶3
细胞培养
癌症研究
化学
K562细胞
NKG2D公司
CD16
细胞因子
细胞生物学
自然杀伤性T细胞
细胞
细胞因子诱导的杀伤细胞
免疫学
CD49b
细胞毒性
白细胞介素
穿孔素
体外
生物化学
白血病
遗传学
作者
Hans Bergman,Christer Lindqvist
出处
期刊:Anticancer Research
[Anticancer Research USA Inc.]
日期:2021-07-01
卷期号:41 (7): 3281-3285
被引量:3
标识
DOI:10.21873/anticanres.15114
摘要
Background/Aim: Recent studies have indicated that natural killer (NK) cells present in peripheral blood mononuclear cells (PBMCs) might be responsible for the somewhat poor outcome of clinical trials conducted with the NK cell line NK-92, as well as chimeric antigen receptor-modified NK-92 cells against leukemias and lymphomas. These NK cells and how their cytotoxic profiles can be altered by some common gamma chain receptor-dependent cytokines or by removal of CD4+ cells have been addressed herein. Materials and Methods: A time-resolved fluorometric assay using 2.2’:6’.2”-terpyridine-6.6”-dicarboxylic acid-labeled NK-92 or K562 as target cells was used for measuring the cytotoxic activity of cytokine-treated PBMCs and purified NK cells. Results: Pre-incubation with 25 ng/ml interleukin 12 (IL-12), IL-15 or IL-21 for 72 h increased NK cell activity against K562 cells by more than 90% (1:25 target:effector ratio), whereas the corresponding NK cell activity against NK-92 cells was reduced by 15.9±0.1% by IL-12 and 50.6±2.9% by IL-15 compared to cells treated with medium alone. IL-7, on the other hand, increased NK activity against K562 to a much smaller extent (10.4±0.4%) and inhibited NK-92 cell lysis by 15.2±0.3%. Interestingly, similar amounts of IL-2 potentiated NK cell activity against both K562 and NK-92 cells by 50.9±0.5% and 14.3±0.9%, respectively. Purification of NK cells with magnetic beads demonstrated that NK cells indeed were responsible for the observed cytotoxic activity against both NK-92 cells (58.5±9.10%, 1:100 target:effector ratio) and K562 cells (81.6±9.57%, 1:100 target:effector ratio). Elimination of CD4+ cells from PBMCs did not alter the NK activity profile. Conclusion: This study highlights a problem that might arise with immune-based NK-92 and chimeric antigen receptor-transduced NK-92 cell therapies and pinpoints the need for evaluating new NK-like cell lines.
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