在CAR T细胞中CCR5和IL-12的共同表达通过重编程固体瘤中的瘤微环境来提高抗瘤功效
Yonggui Tian1,2, Liubo Zhang1, Yu Ping1
1Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Cancer immunology, immunotherapy : CII
|January 3, 2025
概括
针对固体瘤的工程化模拟抗原受体 (CAR) T 细胞显示出更好的透和有效性. 同时表达CR5和IL-12可以增强CAR-T细胞的迁移,并克服瘤透巨细胞的免疫抑制.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 癌症治疗 癌症治疗
背景情况:
- 固体瘤对CAR T细胞疗法构成挑战,包括透不良和免疫抑制瘤微环境.
- 像CCL4,CCL5和它们的受体CCR5这样的关键化学因子与瘤中T细胞透有关.
- 透瘤的巨细胞可以抑制CD8+ T细胞的抗瘤反应.
研究的目的:
- 通过解决透和免疫抑制,为固体瘤开发增强的CAR T细胞.
- 研究CCL4/CCL5-CCR5轴在CAR T细胞迁移中的作用.
- 评估IL-12分泌对抗巨细胞介导免疫抑制的潜力.
主要方法:
- 利用癌症基因组图谱数据库来识别关键的化学因子.
- 工程化针对美索林的CAR T细胞,以共同表达CCR5和IL-12 (CARTmeso-5-12).
- 在食道癌模型中评估工程CAR T细胞的体外和体外抗瘤能力.
主要成果:
- 在CAR T细胞中增强的CCR5表达改善了瘤透.
- 通过CAR T细胞分泌的IL-12减弱了巨细胞介导的免疫抑制.
- CARTmeso-5-12细胞在体外和体内表现出优异的瘤根除能力.
结论:
- 在CAR T细胞中CCR5和IL-12的联合表达代表了克服固体瘤微环境障碍的有希望的策略.
- 这种双重工程的CAR T细胞方法增强了T细胞的迁移和功能,从而改善了瘤根除.
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