在患有癌症和自身免疫性疾病的患者中,高免疫性CD19CAR T细胞逃避了全排斥
Xiaomeng Hu1, Pascal Beauchesne1, Chenyan Wang1
1Sana Biotechnology Inc., 1 Tower Place, South San Francisco, CA, USA.
Cell stem cell
|August 14, 2025
概括
在临床试验中,具有低免疫 (HIP) 编辑的工程CAR T细胞成功避免了免疫排斥. 这一进步支持开发通用,现成的CAR T细胞疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞疗法细胞疗法
- 在瘤学瘤学.
背景情况:
- 现成的CAR T细胞需要克服异性免疫反应的策略,以便在广泛的临床应用中.
- 目前的CAR T细胞疗法往往是自的,限制了可访问性和增加成本.
研究的目的:
- 评估正在接受治疗的患者对HP编辑的CD19 CAR T细胞 (SC291) 的免疫反应.
- 评估低免疫 (HIP) 编辑策略在预防全排斥方面的有效性.
主要方法:
- 从ARDENT和GLEAM临床试验中进行了探索性免疫分析.
- SC291细胞被设计成具有CD19 CAR,TRAC淘汰,HLA枯竭和CD47过度表达的SC291细胞.
- 监测了免疫反应,抗体发育和B细胞枯竭.
主要成果:
- 在所有患者和剂量中,没有观察到对完全HIP编辑的SC291 CAR T细胞的新免疫反应.
- 针对SC291.1.的HLA-replete亚种群,观察到一种与免疫反应相关的反应.
- 缺乏抗HLA复制CAR T细胞抗体与深度CD19+细胞枯竭和外围B细胞枯竭相关.
结论:
- 低免疫 (HIP) 编辑策略可靠地规避对CAR T细胞的全原性免疫反应.
- HIP编辑是开发通用,现成的CAR T细胞疗法的有前途的方法.
- 临床数据支持HIP编辑的CAR T细胞在癌症治疗中克服免疫障碍的潜力.
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