开发一种新型的HER2-CAR单细胞细胞疗法,具有可控制的增殖和增强的抗瘤疗效
Bing Yang1,2, Xiaoxue Wang3, Xundong Wei2
1Peking University Fifth School of Clinical Medicine, Beijing 100730, China.
Chinese medical journal
|January 20, 2024
概括
工程化化学抗原受体单细胞 (CAR-M) 有效向HER2阳性瘤,并增强T细胞透. 这种新的CAR-THP1疗法对组合治疗有前途,改善了抗瘤免疫反应.
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:
- 免疫细胞透到瘤中的不足限制了CAR-T细胞治疗的有效性.
- 由于瘤微环境的丰富,CAR-单细胞/巨细胞 (CAR-M) 显示出潜力.
- 开发了一种新的CAR-M来增强T细胞和免疫细胞的透.
研究的目的:
- 构建和评估一种新的仿真抗原受体单细胞 (CAR-M) 疗法.
- 评估CAR-THP1.1的抗瘤疗效和免疫细胞透能力.
- 探索CAR-THP1与其他免疫细胞结合的协同潜力.
主要方法:
- 可诱导的caspase-9 (iCasp9) 和HER2 CAR元素通过lentivirus转移到THP1细胞中.
- 使用流式细胞计,Incucyte和小鼠模型评估自杀效率和抗瘤有效性.
- 转录组测序以分析信号通路和评估与RAK细胞结合的CAR-THP1.
主要成果:
- 一种包含iCasp9,CD3ζ和CD147的新型CAR-THP1证明了受控的增殖和特定的抗瘤疗效.
- CAR-THP1分化为M1表型,弥合先天性和适应性免疫.
- 使用CAR-THP1和RAK细胞的组合疗法通过降解瘤基质并促进T细胞透,提高了治疗效率.
结论:
- CAR-THP1对HER2阳性瘤表现出有效性.
- CAR-THP1显示出与其他免疫细胞结合治疗的显著潜力.
- 这种方法增强了抗瘤免疫反应和免疫细胞透.
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