抑制JNK增强了CAR-T细胞的细胞毒性
bioRxiv : the preprint server for biology
|August 20, 2025
概括
向c-Jun N-终端酶 (JNK) 增强了对固体瘤的仿真抗原受体T (CAR-T) 细胞治疗. 通过调节激活T细胞的核因子 (NFAT),抑制JNK增强了CAR- T细胞的抗瘤活性.
科学领域:
- 免疫学
- 癌症生物学
- 细胞治疗
背景情况:
- 化学抗原受体T (CAR-T) 细胞治疗对固体瘤具有前景.
- 激活T细胞的核因子 (NFAT) 对T细胞功能至关重要.
- 向c-Jun N-终端激酶 (JNK) 可能会提高CAR-T细胞的疗效.
研究的目的:
- 研究JNK在CAR-T细胞功能中的作用.
- 确定抑制JNK是否可以改善CAR- T细胞的抗瘤活性.
- 阐明JNK影响CAR-T细胞性能的机制.
主要方法:
- 在CAR-T细胞中开发出对JNK的短毛针RNA (shRNA).
- 从人类外周血液中生成的向HER2的CAR- T细胞.
- 在试验室和人类卵巢癌异种移植模型中评估功能.
主要成果:
- 抑制了抗原诱导的刺激和细胞因子的产生.
- 在体外和体内增强JNK抑制的抗瘤细胞毒性.
- 通过依赖NFATc1的途径增加了JNK的表达.
结论:
- JNK信号显著调节了CAR-T细胞的毒性.
- 抑制JNK是提高CAR-T细胞有效性的潜在策略.
- 这种方法可以改善人类癌症患者的治疗结果.
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