开发抗小鼠IL-18结合蛋白抗体,以刺激IL-18生物活性
Arnaud Huard1,2,3, Sébastien Fauteux-Daniel1,2,3, Jérémie Goldstein1,2,3
1Division of Rheumatology, Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Journal of immunology (Baltimore, Md. : 1950)
|February 28, 2025
概括
研究人员开发了一种中和抗体,该抗体的向是介素-18结合蛋白 (IL-18BP). 这种抗体增强了INTERLEUKIN-18 (IL-18) 的活性,显示出增强对疾病的免疫反应的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞因子生物学 细胞因子生物学
- 抗体工程 抗体工程
背景情况:
- 介素-18 (IL-18) 是T助手1和细胞毒性免疫反应的关键细胞因子.
- IL-18活性受到IL-18结合蛋白 (IL-18BP) 的严格调节,IL-18是一种诱受体.
- 失调IL-18/IL-18BP平衡可能导致系统性炎症,如巨细胞激活综合征 (MAS) 中所见.
研究的目的:
- 开发和描述针对小鼠IL-18BP的新型单克隆抗体.
- 识别具有针对IL-18BP的特定中和活性的抗体.
- 评估中和抗IL-18BP抗体在促进IL-18介导免疫反应中的治疗潜力.
主要方法:
- 一组子单克隆抗老鼠IL-18BP抗体的生成.
- 三明治ELISA和IL-18生物测试以评估抗体结合和IL-18BP抑制功能.
- 使用CpG诱导的MAS模型和IL-18BP淘汰小鼠进行体内研究,以评估抗体的有效性和特异性.
主要成果:
- 产生了几种抗IL-18BP抗体,对IL-18BP具有不同程度的对抗性.
- 抗体445表现出强大的中和活性,从IL-18BP复合体释放IL-18.
- 服用抗体445加剧了CpG诱导的MAS,证实了其在体内增强IL-18活性的能力.
结论:
- 成功开发了一种针对IL-18BP的中和单克隆抗体 (445).
- 这种抗体通过破坏IL-18-IL-18BP相互作用,有效地促进IL-18活性.
- 用中和抗体向IL-18BP是一种有前途的策略,可以在各种条件下增强免疫反应.
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