不同的Fc受体激活驱动了一种抗瘤疫苗效应
David J DiLillo1, Jeffrey V Ravetch1
1Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Cell
|May 16, 2015
概括
单克隆抗体 (mAbs) 可以触发长期的抗瘤免疫力. 对抗原呈现细胞,特别是树突细胞 (DCs) 的Fc受体 (FcγR) 接触对于这种疫苗效应至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 抗体工程 抗体工程
背景情况:
- 抗瘤单克隆抗体 (mAbs) 通过抗体依赖细胞毒性 (ADCC) 诱导短期瘤细胞杀死.
- 抗瘤mAb疗法还可以建立长期的抗瘤免疫反应,称为疫苗效应.
- 这种疫苗效应的产生背后的机制仍然不完全理解.
研究的目的:
- 阐明抗瘤单克隆抗体产生长期疫苗效应的机制.
- 研究Fc马受体 (FcγRs) 在介导抗原呈现细胞的抗瘤细胞免疫中的作用.
- 为了确定ADCC和诱导疫苗效应所需的特定FcγR相互作用.
主要方法:
- 利用小鼠模型研究抗瘤疫苗对模型新抗原的效果.
- 使用FcγR人性化的小鼠来评估人类的FcγR参与.
- 研究了FcγR表达在CD11c(+) 抗原呈现细胞和树突细胞 (DC) 上的作用.
主要成果:
- 在CD11c(+) 抗原呈现细胞上的FcγR表达对于产生ADCC后的抗瘤T细胞反应至关重要.
- 抗瘤人类IgG1 (hIgG1) 需要人类FcγRIIIA (hFcγRIIIA) 参与ADCC的巨细胞.
- 诱导强大的疫苗效应需要人类FcγRIIA (hFcγRIIA) 在树突细胞 (DC) 上的hIgG1参与.
结论:
- 抗瘤mAbs诱导的疫苗效应依赖于FcγR与抗原呈现细胞的接触.
- 虽然hFcγRIIIA是ADCC的关键,但DC上的hFcγRIIA对于刺激长期抗瘤细胞免疫力至关重要.
- 针对细胞毒性有效性 (hFcγRIIIA结合) 和DC激活 (hFcγRIIA结合) 优化抗体对于有效的癌症免疫疗法至关重要.
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