实验室烧瓶
外周血单个核细胞
免疫疗法
细胞毒性T细胞
癌症免疫疗法
过继免疫治疗
生物反应器
细胞
自然杀伤细胞
免疫学
癌症研究
细胞疗法
化学
生物
体外
免疫系统
生物化学
物理化学
有机化学
作者
Tolga Sütlü,Birgitta Stellan,Mari Gilljam,Hernán Concha Quezada,Hareth Nahi,Gösta Gahrton,Evren Alici
出处
期刊:Cytotherapy
[Elsevier]
日期:2010-12-01
卷期号:12 (8): 1044-1055
被引量:112
标识
DOI:10.3109/14653249.2010.504770
摘要
Natural killer (NK) cell-based adoptive immunotherapy is a promising approach for the treatment of cancer. Ex vivo expansion and activation of NK cells under good manufacturing practice (GMP) conditions are crucial for facilitating large clinical trials. The goal of this study was to optimize a large-scale, feeder-free, closed system for efficient NK cell expansion.Peripheral blood mononuclear cells (PBMCs) from healthy donors and myeloma patients were cultured for 21 days using flasks, cell culture bags and bioreactors. Final products from different expansions were evaluated comparatively for phenotype and functionality.Significant NK cell expansions were obtained in all systems. The bioreactor yielded a final product rich in NK cells (mean 38%) ensuring that a clinically relevant cell dose was reached (mean 9.8 x 10⁹ NK cells). Moreover, we observed that NK cells expanded in the bioreactor displayed significantly higher cytotoxic capacity. It was possible to attribute this partially to a higher expression level of NKp44 compared with NK cells expanded in flasks.These results demonstrate that large amounts of highly active NK cells for adoptive immunotherapy can be produced in a closed, automated, large-scale bioreactor under feeder-free current GMP conditions, facilitating clinical trials for the use of these cells.
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