扩展的适应性NKG2C+NK细胞表现出强大的ADCC和对HBV感染的肝瘤细胞系的功能反应
Jonida Kokiçi1, Helena Arellano-Ballestero2, Benjamin Hammond3
1Division of Infection and Immunity, UCL, London, UK.
Cytotherapy
|December 9, 2025
概括
研究人员成功地扩展了从慢性乙型肝炎病毒 (HBV) 感染的患者身上获得的适应性自然杀手 (NK) 细胞. 这些增强的NK细胞显示出治疗HBV相关肝病和癌症的前景.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 细胞疗法细胞疗法
背景情况:
- 乙型肝炎病毒 (HBV) 感染导致慢性肝病和肝细胞癌 (HCC).
- 自然杀手 (NK) 细胞与HBV感染的细胞作斗争,但在慢性感染中,它们的功能受损.
- 适应性NK细胞 (NKG2C+) 具有改善抗HBV免疫力和治疗由HBV驱动的癌症的潜力.
研究的目的:
- 扩展具有慢性HBV感染的个体的自适应性NK细胞,有或没有HIV联合感染.
- 评估扩展适应性NK细胞对肝瘤细胞系的表型,细胞毒性和功能能力.
- 调查TGF-β预条件的潜力,以诱导适应性NK细胞中的组织居民特征,用于肝脏向免疫治疗.
主要方法:
- 使用K562-HLA-E料细胞和IL-2用于从冷保存的PBMC中适应性NK细胞扩张.
- 评估了适应性NK细胞表型 (NKG2C,Granzyme B,CD16,CD2),ADCC,以及对肝瘤细胞系的功能.
- 评估了TGF-β预条件对组织内标记物 (CD103,CD49a) 和NK细胞对自身T细胞的反应性的影响.
主要成果:
- 达到>97%的纯度和适应性NK细胞的100倍扩张,具有高NKG2C和Granzyme B表达.
- 扩张的NK细胞表现出增强的ADCC和对各种肝瘤细胞系的功能反应.
- 在TGF-β预条件诱导的组织内标记物中,同时保持NK细胞的功能,对自身T细胞的反应性最小.
结论:
- 从长期感染HBV的捐赠者中首次成功扩展功能适应性NK细胞.
- 这种扩展方法为NK细胞治疗HBV感染和相关癌症提供了一个平台.
- 与单克隆抗体结合疗法的潜力,以实现HBV功能治愈和治疗HBV驱动的恶性瘤.
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