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乳酸改善了Treg制造和in vivo功能.
Karoliina Tuomela1,2, Emily S Y Leong1,2, Manjurul Haque1,2
1Department of Surgery, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
Molecular therapy. Methods & clinical development
|October 28, 2025
概括
乳酸 (LA) 增强细胞治疗的调节性T细胞 (Tregs) 的纯度,活力和抑制功能. 这种方法在临床前模型中提高了Treg稳定性和有效性,为治疗自身免疫性疾病和移植排斥提供了有前途的方法.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞疗法细胞疗法
- 生物化学 生物化学
背景情况:
- 使用调节性T细胞 (Tregs) 的采用细胞疗法显示出对自身免疫和移植的希望.
- 扩大纯和高度抑制的Tregs仍然是细胞疗法开发中的一个重大挑战.
- 已知乳酸 (LA) 在瘤微环境中增强Treg功能.
研究的目的:
- 研究乳酸 (LA) 在调节性T细胞 (Tregs) 扩张过程中的潜在益处.
- 为了确定LA是否提高Treg纯度,活力,抑制功能,并减少疲劳标记.
- 在免疫媒介疾病的临床前模型中评估LA条件Tregs的疗效.
主要方法:
- 人类多克隆和仿制抗原受体 (CAR) -Tregs被扩展,有或没有乳酸 (LA).
- 在扩张后和重新刺激时评估了Treg活力,纯度,糖解和抑制功能.
- 在CAR-Tregs中分析了疲劳标记 (PD-1, TIM-3, LAG-3, TOX, BLIMP-1) 的表达.
- 在慢性刺激和异源移植对宿主疾病的免疫缺陷小鼠模型中测试了LA调节的Tregs.
主要成果:
- 从第3天开始添加LA显著改善了Treg活力和纯度.
- 在重新刺激后,LA增强了Treg糖解,并导致了优越的抑制功能.
- 在CAR-Tregs中,LA降低了与疲劳标记的性信号相关表达.
- 在LA条件下的Tregs在小鼠模型中显示出增强的稳定性,减少疲劳,并提高有效性.
结论:
- 乳酸 (LA) 对人类Treg扩张和细胞治疗功能的多式有益作用.
- LA提高了Treg的纯度,活力和抑制能力,同时减轻了疲.
- LA代表了一种创新方法,用于产生最佳的Treg产品,用于自身免疫和移植的治疗应用.
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