选择T细胞来源决定了神经母细胞瘤中CAR-T细胞的活性
Lorena García-García1,2, Elena G Sánchez1,2, Mariya Ivanova1,2
1Department of Pediatric Hematology and Oncology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Frontiers in immunology
|April 11, 2024
概括
这项研究开发了一种新的仿真抗原受体-T细胞 (CAR-T) 疗法,使用GD2特异性抗体向神经母细胞瘤. 来自带血的CAR-T细胞显示出有前途的抗瘤活性,表明固体瘤治疗的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 细胞疗法细胞疗法
背景情况:
- 化学抗原受体-T细胞 (CAR-T) 疗法在血液恶性瘤中取得了成功,但由于抗原稀缺,在固体瘤中面临挑战.
- 神经母细胞瘤 (NB) 表达GD2,一种可向抗原,使其成为CAR-T治疗的潜在候选者.
研究的目的:
- 开发和评估一种针对神经母细胞瘤的新型组合性CAR-T细胞策略,针对GD2.2.
- 为了比较不同的T细胞来源 (带血液和外围血液) 和培养条件,以获得最佳的CAR-T细胞生产.
主要方法:
- 一个多功能抗FITC CAR-T效应器系统与FITC结合抗GD2抗体 (Dinutuximab) 结合,用于NB向.
- 用IL-7+IL-15+IL-21和CD3/CD28刺激培养了带血 (CB) 和富含CD45RA的外周血液 (45RA) T细胞.
- 鉴定包括免疫表型,载体拷贝数和基因组完整性.
- 在体外功能通过与NB细胞系的共同培养试验进行了评估.
主要成果:
- IL-7+IL-15+IL-21细胞因子尾酒促进了有利的增殖,并保持了CB和45RAT细胞中差异较小的表型.
- 来自CB的抗FITC CAR-T细胞表现出辅助刺激受体 (OX40,4-1BB) 的增强表达,并释放出更高水平的IFN-γ和TNF-α.
- 与CB衍生的CAR-T细胞共同培养,在48小时内将NB细胞活力降低了高达70%.
结论:
- 带血和富含CD45RA的T细胞是CAR-T细胞生产的可行的全源来源.
- 用IL-7+IL-15+IL-21进行体外培养可能会增强CAR-T细胞的持久性.
- 这种结合性CAR-T策略有望在NB治疗中补充dinutuximab.
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