由于Cbl诱导HER2的无处可见性,使免疫系统从HER2向的CAR-T中逃脱出来
Yanqiu Yang1, Qingqing Sun2, Zhiping Deng3
1Department of Ultrasonography, The Fifth People's Hospital of Qinghai Province, Qinghai, China.
Journal of biochemical and molecular toxicology
|June 24, 2023
概括
针对HER2-阳性乳腺癌 (BC) 的化学抗原受体T细胞 (CAR-T) 治疗显示出有前途. 将HER2-CAR-T与PD-L1免疫疗法结合起来,可以增强抗瘤效果,克服复发机制.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 在乳腺癌 (BC) 中,高HER2表达与复发率增加和预后较差相关.
- 免疫疗法是治疗HER2阳性BC的有希望的途径.
- 了解免疫细胞通路和复发机制对于有效治疗至关重要.
研究的目的:
- 开发和评估HER2特定的化学抗原受体T细胞 (CAR-T) 治疗HER2阳性BC的治疗方法.
- 研究PD-L1免疫疗法作为HER2-CAR-T疗法的辅助剂的作用.
- 阐明免疫治疗后BC复发背后的分子机制,重点关注cbl的HER2调节.
主要方法:
- 使用逆转录病毒构建了HER2-CAR-T细胞.
- 在体外和体内实验验验证了HER2-CAR-T细胞的特定识别和抗瘤作用.
- 在瘤细胞或树突细胞中的PD-L1敲击和巨细胞枯竭被用来研究免疫路径.
- 免疫沉,泛定位测试和等离子体分析确定了CBL介导的HER2的负调节.
主要成果:
- HER2-CAR-T细胞在体外和体内专门识别并抑制了HER2-阳性BC细胞.
- 辅助抗PD-L1疗法显著提高了HER2-CAR-T的治疗疗效.
- HER2-CAR-T疗法与树突细胞中的PD-L1敲击相结合,导致了固体瘤的完全根除.
- 复发的瘤表现出由于cbl上调调的HER2表达减少,这表明免疫疗法耐药性的机制.
结论:
- HER2-CAR-T疗法证明了对HER2-阳性细胞的特定向,并调解了抗瘤免疫反应.
- 与PD-L1免疫疗法同时使用,特别是PD-L1在树突细胞中的敲除,可以增强HER2-CAR-T的疗效.
- 了解CBL介导的HER2调节是克服复发性乳腺癌免疫疗法耐药性的关键.
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