利用瘤酸度:创新的乳酸反应促进剂能够精确控制固体瘤中CAR-T细胞活性
Meiqi Feng1, Linxia Zhang1, Qibin Liao2,3
1Institutes of Biomedical Sciences & Clinical Center of Biotherapy at Zhongshan Hospital, Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, China.
Journal for immunotherapy of cancer
|February 10, 2026
概括
工程CAR-T细胞使用乳酸向瘤,提高效率和安全性. 这种新的方法通过控制酸性瘤环境中的活性来增强癌症免疫疗法.
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:
- 固体瘤由于乳酸积累而表现出酸性瘤微环境 (TME).
- 这种酸度损害了仿真抗原受体-T (CAR-T) 细胞功能,并增加了点外瘤毒性 (OTOT).
研究的目的:
- 开发一种使用乳酸作为瘤特异性触发器的新型CAR-T技术.
- 实现精确控制CAR活性,以提高抗瘤疗效和减少OTOT.
主要方法:
- 设计了一种乳酸响应促进剂 (LARP),并将其集成到向HER2的CAR-T细胞中.
- 量化CAR表达,评估了体外细胞毒性,并在人性化小鼠模型中评估了体内抗瘤疗效和OTOT.
主要成果:
- 在酸性条件下,LARP成功地增加了CAR表达,增强了体外瘤杀死.
- 在体内,LAR CAR-T细胞表现出可比的瘤根除,安全性显著改善,包括缺少肝毒性和最小的目标外毒性.
结论:
- LARP策略精确地控制了酸性TME中的CAR-T细胞活性,克服了有效性和安全性的障碍.
- 这种乳酸感应的CAR-T平台为固体瘤免疫治疗提供了临床可翻译的方法.
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