发展用于自然杀伤细胞扩增的基因工程饲养细胞。
Development of Genetically Engineered Feeder Cells for Natural Killer Cell Expansion.
发表日期:2023 Sep
作者:
DA Yeon Lee, Yeongrin Kim, Jin Song Park, Ji U Choi, Hye Gwang Jeong, Chi Hoon Park
来源:
PHARMACOLOGY & THERAPEUTICS
摘要:
为了获取足够数量且高质量的自然杀伤细胞(NK细胞),我们采用了合成生物学技术开发了供给细胞。将K562细胞工程改造以表达膜结合的IL-2(mbIL2)或IL-13(mbIL13)。将从外周血单个核细胞(PBMCs)中分离的人类原代NK细胞与这些供给细胞共同培养,与K562母细胞相比,显著增加了激活的NK细胞的数量。通过流式细胞术(FACS)分析,显示在K562-mbIL2或mbIL13细胞上扩增的NK细胞表面丰富了NKG2D激活受体。与用正常K562细胞培养的NK细胞相比,K562-mbIL2或mbIL13细胞扩增的NK细胞对癌细胞的溶解作用更加有效。利用与我们的供给细胞共同培养的NK细胞,我们开发了抗CD19嵌合抗原受体(CAR)-NK细胞。它们对CD19阳性癌细胞系表现出强大的细胞毒作用。我们的新开发的供给细胞可以为NK细胞疗法提供有用的工具。版权所有© 2023国际抗癌研究所(George J. Delinasios 博士)。
To obtain sufficient numbers of high-quality natural killer (NK) cells, we developed feeder cells using synthetic biology techniques.K562 cells were engineered to express membrane bound interleukin-2 (mbIL2) or interleukin-13 (mbIL13).The incubation of human primary NK cells isolated from peripheral blood mononuclear cells (PBMCs) with these feeder cells significantly increased the number of activated NK cells compared to K562 parental cells. Fluorescence-activated cell sorting (FACS) analysis demonstrated that NKG2D activating receptors were abundant on the surface of NK cells expanded by K562-mbIL2 or mbIL13 cells. NK cells expanded on K562-mbIL2 or mbIL13 lysed cancer cells more effectively than those cultured with normal K562 cells. Using NK cells incubated with our feeder cells, we developed anti-CD19 chimeric antigen receptor (CAR)-NK cells. They showed robust cytotoxic effect against CD19 positive cancer cell line.Our newly developed feeder cells could provide useful tools for NK cell therapy.Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.