针对转移性侵袭性甲状腺癌的优化CART细胞疗法
bioRxiv : the preprint server for biology
|December 3, 2025
概括
我们开发了针对甲状腺刺激激素受体 (TSHR) 向的嵌合抗原受体T (CART) 细胞疗法用于甲状腺癌. 将TSHR-CART细胞与MAPK抑制剂结合起来,通过恢复TSHR表达来增强对攻击性,分离的瘤的疗效.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 分子生物学分子生物学
背景情况:
- 甲状腺癌的死亡率与侵略性的转移性瘤有关.
- 化学抗原受体T (CART) 细胞疗法看起来很有前途,但面临着目标下调等挑战.
- 甲状腺刺激激素受体 (TSHR) 是差异化甲状腺癌的点.
研究的目的:
- 开发和评估一种新型的TSHR向性CART细胞疗法,用于攻击性甲状腺癌.
- 调查组合策略,以克服TSHR下调在脱差甲状腺癌.
- 评估将TSHR-CART细胞与基因激活蛋白激酶 (MAPK) 抑制剂结合的疗效.
主要方法:
- 开发针对TSHR的CART细胞.
- 在体外和体内对TSHR+细胞系和患者衍生的异种移植进行体外和体内测试.
- 使用TSHR-CART细胞和MAPK抑制剂进行组合治疗.
主要成果:
- TSHR-CART细胞表现出抗原特异激活和抗瘤作用.
- 不分化的甲状腺癌显示TSHR降低调节.
- 与单独治疗相比,组合疗法显著增加了TSHR表达,增强了抗瘤疗效,并在异种移植中延长了生存时间.
结论:
- TSHR-CART细胞疗法是对差异化甲状腺癌的潜在治疗方法.
- MAPK 抑制剂可以恢复 TSHR 表达在非分化甲状腺癌.
- 使用TSHR-CART细胞和MAPK抑制剂的组合疗法提供了对抗侵袭性甲状腺癌的有效策略.
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