抑制AXL可以改善化学抗原受体T细胞的抗瘤活性
R Leo Sakemura1,2, Mehrdad Hefazi1,2, Michelle J Cox1
1T Cell Engineering, Mayo Clinic, Rochester, Minnesota.
Cancer immunology research
|June 28, 2023
概括
抑制AXL可以增强仿真抗原受体T (CAR T) 细胞治疗的疗效. 阻断AXL向免疫抑制细胞,改善CAR T细胞功能,克服对癌症免疫疗法的抵抗力.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 受体氨酸激酶AXL与癌症进展和免疫疗法耐药性有关.
- 免疫抑制细胞中的AXL表达减少了像CAR T细胞疗法这样的免疫疗法的有效性.
研究的目的:
- 研究AXL抑制的潜力,作为一种克服对仿真抗原受体T (CAR T) 细胞疗法的抗性策略.
- 为了确定AXL抑制对CD19向的CAR T (CAR T19) 细胞功能的影响.
主要方法:
- 在T细胞和CART细胞中评估了AXL表达.
- 利用小分子抑制剂和遗传干扰来抑制T细胞中的AXL.
- 评估了AXL抑制对CAR T细胞效应因子功能和细胞因子产生的影响.
主要成果:
- T细胞和CART细胞,特别是激活的Th2CART细胞和M2极化巨细胞,表达高水平的AXL.
- 抑制AXL有选择性地影响Th2 CAR-T细胞,减少Th2细胞因子,并逆转CAR-T细胞的抑制.
- 抑制AXL促进了CAR T细胞效应器功能.
结论:
- 抑制AXL是一种有前途的策略,可以提高CAR T细胞治疗的疗效.
- 抑制AXL通过双重机制起作用:向Th2细胞,并逆转肌肉质诱导的CAR T细胞的抑制.
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