从盘子中采用细胞疗法:增强诱导多能干细胞的潜能
Pieter L Lindenbergh1,2, Sjoukje J C van der Stegen1
1Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
概括
诱导多能干细胞 (iPSCs) 为采用细胞疗法 (ACT) 提供了替代的全源源,产生了在很大程度上模仿外周血液单核细胞 (PBMC) 衍生的细胞的免疫效应剂. 工程iPSC衍生细胞增强了它们的抗瘤能力,用于临床应用.
科学领域:
- 免疫学 免疫学 免疫学
- 干细胞生物学 干细胞生物学
- 细胞疗法细胞疗法
背景情况:
- 自主采用细胞疗法 (ACT) 在临床上取得了成功,但在细胞质量,数量和个性化制造方面面临局限性.
- 诱导多能干细胞 (iPSCs) 通过分化为各种免疫作用因子,为ACT提供了替代的全源细胞来源.
- 将iPSC衍生的免疫效应剂与外围血液单核细胞 (PBMC) 衍生的对应物进行比较,对于推进ACT至关重要.
研究的目的:
- 为了比较iPSC衍生的免疫作用因子及其PBMC衍生的对应物的特征和功能.
- 审查IPSC衍生ACT产品目前的临床前和临床开发状态.
- 突出iPSCs在产生工程免疫效应剂以增强抗瘤活性方面的潜力.
主要方法:
- 细胞表面标记物表达和细胞毒性效应因子功能的比较,用于iPSC和PBMC衍生的免疫细胞 (T细胞,NK细胞,巨细胞,中性粒细胞) 之间.
- 在临床前和临床开发中对iPSC衍生ACT产品的审查.
- 分析工程策略,以增强iPSC衍生的免疫因子的抗瘤能力.
主要成果:
- 从iPSC衍生的T细胞,NK细胞,巨细胞和中性粒细胞在很大程度上复制了它们从PBMC衍生的对应细胞的功能.
- 设计的iPSC衍生免疫效应器可以配备嵌合式抗原受体,用于向瘤细胞杀死.
- iPSC和PBMC衍生细胞之间的差异需要进一步的工程来获得最佳的抗瘤疗效.
结论:
- 可以设计iPSC来产生具有同质特异性的免疫效应剂,并为ACT增强功能.
- 特定于TAA和增强的iPSC衍生的T和NK细胞正在临床试验中,而巨细胞和中性粒细胞正在临床前开发中.
- 来自iPSC的免疫效应剂对克服ACT当前的局限性具有显著的前景.
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