铁氨酸激酶信号-独立于MET向与CAR-T细胞
Anna Qin1, Yuan Qin1, Joseph Lee2
1Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA.
Journal of translational medicine
|October 1, 2023
概括
特定于MET的CAR T细胞显示出对肝细胞癌 (HCC) 治疗的前景. MET-CAR.CD28ζ T细胞表现出优异的抗瘤活性,但也增加了疲劳,需要进一步研究以获得最佳疗效.
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:
- 肝细胞癌 (HCC) 经常过度表达MET受体氨酸激酶.
- 目前的MET抑制剂因需要活性MET信号而受到限制,使患者选择复杂化.
- 化学抗原受体 (CAR) T细胞疗法提供了一种潜在的策略,以向MET过度表达的HCC,无论MET激活状态如何.
研究的目的:
- 开发和评估针对肝细胞癌 (HCC) 的MET特异性CAR T细胞.
- 在临床前模型中,比较MET-CAR T细胞与不同协同刺激域 (CD28ζ与4-1BBζ) 的疗效.
主要方法:
- 使用CD28ζ或4-1BBζ共刺激领域构建了MET特异的CAR T细胞.
- 卡尔T细胞活性,细胞因子释放和瘤抑制在体外和体内使用HCC细胞系和正位异种移植模型进行了评估.
主要成果:
- 在体外,MET-CAR T细胞有效地杀死了MET-阳性HCC细胞.
- 与MET-CAR.4-1BBζ T细胞相比,MET-CAR.CD28ζ T细胞表现出更高的细胞因子释放和PD-1表达.
- 在体内,MET-CAR.CD28ζ T 细胞表现出优异的抑制 HCC 瘤生长.
结论:
- 特定于MET的CAR T细胞可以针对MET过度表达的HCC,而不管MET激活.
- MET-CAR.CD28ζ T细胞具有更大的抗HCC功效,但容易导致T细胞耗尽.
- 需要进一步的策略来缓解T细胞耗尽,以提高MET-CART细胞在体内治疗的疗效.
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