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细胞因子影响自然杀手细胞表型和功能,对质母细胞瘤in vitro产生影响

Minna Sivonen^1,2, Katja A Sirviö¹, Sara Wojciechowski¹

¹Kuopio Center for Gene and Cell Therapy, Kuopio, Finland.

Frontiers in immunology

|October 16, 2023

概括

这项研究优化了天然杀手 (NK) 细胞扩张用于质母细胞瘤免疫疗法. 最好的方案使用特定的细胞因子组合和激活方法来增强NK细胞的细胞毒性和制造潜力.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
癌症研究癌症研究

背景情况:

自然杀手 (NK) 细胞对于天生的免疫力和癌症监测至关重要.
NK细胞提供了针对质母细胞瘤的全源性,现成的免疫疗法的潜力.
优化NK细胞扩张对于临床应用至关重要.

研究的目的:

确定针对细胞毒性NK细胞针对质母细胞瘤的最佳基于细胞因子的,无料激活和扩张协议.
根据生存能力,功能,扩张率和纯度来评估NK细胞扩张条件.
评估扩大NK细胞对质瘤细胞系的细胞毒性和脱粒化.

主要方法:

从外围血液中丰富NK细胞,并使用各种激活和细胞因子组合扩展了16天.
评估了39种不同的条件,包括磁性细胞选择,激活协议 (预激活,重新激活,提升) 和细胞因子尾酒 (IL-2/15,IL-21/15,IL-27/18/15,IL-12/18/15).
细胞毒性和脱粒化被测量在与人类质瘤细胞系的共同培养中.

主要成果:

使用连续的CD3+细胞耗尽和CD56+细胞丰富,实现了最高的扩张率和纯度.
通过IL-12/18/15细胞因子进行预激活,产生了细胞因子诱导的类似记忆的NK细胞,在重新激活时增加了细胞毒性.
在扩张结束时用IL-12/18/15或IL-21/15进行增强,产生了最有细胞毒性的NK细胞,减少了捐赠者的变异性.

结论:

NK细胞的活体增殖和功能取决于供体,起始物质,细胞因子和激活协议.
细胞因子显著改变NK细胞的表型和功能,影响对质瘤的反应性.
这些发现为扩大临床NK细胞制造用于质母细胞瘤治疗提供了基础.

关键词:

细胞因子细胞因子质母细胞瘤 (glioblastoma) 是一种免疫疗法免疫疗法类似于记忆的自然杀手细胞.自然杀手细胞是自然杀手细胞.

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