卡尔-T细胞扩张平台产生了不同的T细胞分化状态
Hannah W Song1, Michaela Prochazkova1, Lipei Shao1
1Department of Transfusion Medicine, Center for Cellular Engineering, National Institutes of Health, Bethesda, MD, USA.
Cytotherapy
|April 16, 2024
概括
制造平台显著影响CAR-T细胞产品质量. 缺氧条件可以维持原始的T细胞表型,这对于工程T细胞治疗的有效性至关重要.
科学领域:
- 细胞免疫疗法细胞免疫疗法
- 生物技术是生物技术.
- 生物工艺工程是生物工艺工程.
背景情况:
- 像CAR-T这样的工程T细胞疗法正在扩展到新的目标和患者群体.
- 扩大CAR-T细胞制造的规模是必不可少的,特别是对于需要更高剂量的固体瘤.
- 制造平台对CAR-T细胞产品表型和功能的影响在很大程度上是未知的.
研究的目的:
- 为了比较四种常见的T细胞制造平台对CAR-T细胞扩张和表型的影响.
- 研究溶解氧水平在制造过程中影响T细胞分化中的作用.
- 确定最佳的制造策略,以保护原始T细胞表型,以提高治疗疗效.
主要方法:
- 四个制造平台 (CliniMACS Prodigy,Xuri,G-Rex,静态袋) 用于相同的培养条件.
- CD4+CD8+T细胞被转化为针对FGFR4.4的CAR.
- 分析了细胞扩张,表型 (例如,CCR7+CD45RA+原始/干部中央记忆细胞),基因表达和新陈代谢.
- 在袋和G-Rex培养物中测试了低氧性状况 (1% O2),以评估它们对T细胞表型的影响.
主要成果:
- 观察到细胞扩张的显著差异,静态袋培养产生了最高的扩张和Prodigy的最低.
- 与袋 (16%) 和G-Rex (13%) 相比,Prodigy平台对原始/干细胞中央记忆类T细胞 (46%) 进行了丰富.
- 奇才CAR-T细胞表现出一种更原始的,更少的细胞毒性和更少的枯竭表型,具有明显的代谢概况.
- 在1%的O2中培养显著增加了原始/干部中央记忆类细胞的百分比 (>60%),这表明氧化影响T细胞分化.
结论:
- 生物反应器系统的选择对CAR-T细胞扩张能力和分化状态产生了深刻的影响.
- 溶解氧水平是制造过程中影响T细胞表型的关键因素.
- 低毒培养条件代表了一种潜在的策略,可以防止T细胞分化,并为CAR-T细胞疗法保留更强大的先天性表型.
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