IL-9作为一种具有最佳JAK/STAT信号传递的自然正交细胞因子,用于工程T细胞治疗
Hua Jiang1,2,3, Sam Limsuwannarot1,3, Kayla R Kulhanek1,4,5,3
1Department of Radiation Oncology, Stanford University School of Medicine. Stanford, CA, 94305, USA.
bioRxiv : the preprint server for biology
|January 27, 2025
概括
使用天然的互乐金-9受体 (IL-9R) 改造的T细胞显示出增强的抗瘤活性和组织透. 这种天然的细胞因子-受体对为T细胞免疫疗法提供了最佳的信号配置.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 癌症治疗 癌症治疗
背景情况:
- 介素-9受体 (IL-9R) 的自然表达有限,这表明有针对性T细胞免疫疗法的潜力.
- 在没有显著免疫调节的小鼠中,高剂量的干白素-9 (IL-9) 可以耐受,这表明了有利的安全性.
研究的目的:
- 研究自然IL-9/IL-9R系统在工程T细胞治疗中的潜力.
- 为了比较与天然IL-9R工程T细胞与合成正交IL-9受体 (o9R) 的疗效.
主要方法:
- 工程T细胞与自然IL-9R,并将其功能与o9R工程T细胞进行比较.
- 分析JAK/STAT信号通路,包括STAT1,STAT3,STAT5和STAT4激活.
- 利用结构引导突变调节IL-9R信号,并评估其对T细胞状态的影响.
主要成果:
- 与o9R相比,与天然IL-9R进行工程的T细胞表现出优异的组织透,干性和抗瘤活性.
- IL-9R信号激活了一个强大的JAK/STAT通路,意外地涉及STAT4,以及STAT1,STAT3和STAT5.
- 特定的IL-9R突变显示STAT1是控制T细胞增殖和分化的平衡的关键调节者.
结论:
- 自然的IL-9/IL-9R细胞因子-受体对具有适合T细胞工程的近直角性质.
- IL-9/IL-9R系统提供了最佳的JAK/STAT信号配置,以提高T细胞治疗的疗效.
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