两个阶段的CD8+CAR T细胞分化在患有大B细胞淋巴瘤的患者
Guoshuai Cao1, Yifei Hu2, Tony Pan1
1Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA.
bioRxiv : the preprint server for biology
|March 31, 2025
概括
针对扩散性大B细胞淋巴瘤的CAR T细胞疗法涉及两个不同的细胞扩张波. 这些波源于不同的前体,影响CAR T细胞持久性和临床结果.
科学领域:
- 免疫治疗是一种免疫疗法.
- 细胞疗法 细胞疗法
- 在瘤学瘤学.
背景情况:
- 化学抗原受体 (CAR) T细胞疗法为扩散型大B细胞淋巴瘤 (DLBCL) 提供了新的治疗途径.
- 了解CAR T细胞分化对于改善患者的治疗结果至关重要,但仍然不完整.
- 艾克西卡巴丁基基洛洛塞尔是用于DLBCL治疗的关键CAR T细胞疗法.
研究的目的:
- 在DLBCL患者中研究CAR-T细胞的体内分化,这些患者接受了Axicabtagene ciloleucel治疗.
- 纵向分析CAR T细胞的克隆扩张,表型和本体发生.
- 阐明CAR T细胞扩张和持久性的背后机制.
主要方法:
- 在CAR T细胞上进行了单细胞,多模式和纵向分析.
- 从DLBCL患者的输液产品和周围血液 (8-28日) 采集了样本.
- 使用内源性TCR克隆类型的血统追踪被用来追踪CAR T细胞起源.
主要成果:
- CD8+ CAR T 细胞表现出两种不同的克隆扩张波.
- 第一个波 (8-14天) 在峰值扩张期间显示了耗尽的效应器记忆表型.
- 第二波 (第21-28天) 在高峰后持续期间显示了终端效应者表型.
- 血统追踪显示,这两个波源于输液产品中的不同前体:第一个波的效应器类,第二个波的茎类.
- 在CAR T细胞种群中的输注前异质性推动了这些独特的扩张波.
结论:
- 卡尔T细胞的扩张和持久性是由克隆,表型和本体特异性的细胞群体介导的.
- 这些独特的CAR T细胞群体在临床疗效方面具有互补的作用.
- 这些发现挑战了在峰值后CAR T细胞收缩仅仅是由于细胞亡或短寿命细胞的扩散的概念.
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