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在采用T细胞治疗中,自我调节的CAR-T细胞调节细胞因子释放综合征
Meng-Yin Lin1, Eunwoo Nam1, Ryan M Shih2
1Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
The Journal of experimental medicine
|April 12, 2024
概括
工程T细胞分泌tocilizumab (Toci) 减少细胞因子释放综合征 (CRS) 在仿真抗原受体 (CAR) -T细胞治疗期间的严重性. 这种自我调节的方法在临床前模型中提高了抗瘤疗效和安全性.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 生物技术是生物技术.
背景情况:
- 细胞因子释放综合征 (CRS) 是化学抗原受体 (CAR) -T细胞疗法的显著不良影响.
- 管理CRS对于提高CAR-T细胞治疗的安全性和适用性至关重要.
研究的目的:
- 开发能够减轻CRS的自我调节T细胞.
- 为了评估 CAR-T 细胞的安全性和有效性,这些细胞被设计为分泌细胞因子抑制剂.
主要方法:
- 开发设计为分泌托西利祖马布衍生的单链可变片段 (Toci) 的CAR-T细胞.
- 在人性化的NSG-SGM3小鼠模型中评估CRS严重性和毒性.
- 在体内分泌Toci和传统CAR-T细胞之间的抗瘤疗效的比较.
- 单细胞RNA测序 (scRNA-seq) 用于分析免疫细胞组成.
主要成果:
- 与对照细胞相比,分泌毒素的CAR-T细胞显著降低了与CRS相关的毒性.
- 托西分泌CAR-T细胞的安全概况优于单剂量全身托西利祖马布的安全概况.
- 托基分泌CD19CAR-T细胞在体内表现出增强的抗瘤疗效.
- scRNA-seq在接受Toci分泌CAR-T细胞治疗的小鼠中发现了细胞毒性T细胞的丰富和记忆T细胞表型的保留.
结论:
- 工程T细胞自我调节炎性细胞因子的生产是一种可行的策略,以提高CAR-T细胞治疗.
- 这种方法提供了潜在的双重好处,即提高了安全性和提高了疗效.
- 托基分泌CAR-T细胞策略代表了癌症免疫治疗的临床兼容性进展.
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