抗体herceptin的变种,在抗原结合部位与HER2和VEGF相互作用
Jenny Bostrom1, Shang-Fan Yu, David Kan
1Department of Protein Engineering, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
概括
研究人员设计了一种新型抗体,能够结合两个不同的蛋白质,即人体表皮生长因子受体2 (HER2) 和血管内皮生长因子 (VEGF). 这种"二合一"抗体显示出新治疗策略的前景.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 抗体-抗原相互作用通常是特定的,遵循一个锁钥匙模式,其中一个抗体与单个抗原结合.
- 单克隆抗体是高度特异性的治疗剂,赫塞的例子是向人体表皮生长因子受体2 (HER2) 的赫塞.
研究的目的:
- 设计和描述一种能够同时结合两个不同的抗原的抗体.
- 研究双抗原结合的结构基础及其治疗潜力.
主要方法:
- 隔离了一种具有双结合能力的Herceptin变体.
- 结晶学和突变性研究以阐明结合界面.
- 在小鼠体内细胞增殖试验和体内瘤进展模型.
主要成果:
- 一种新型抗体bH1被开发出来,它能够以高亲和力结合HER2和血管内皮生长因子 (VEGF).
- 结构分析显示,不同的氨基酸残留物与每个抗原接触,在抗体的结合表面有显著的重叠.
- 一种增强的bH1变种在临床前模型中有效抑制了HER2和VEGF驱动的细胞增殖和瘤生长.
结论:
- 这项研究提出了一个
- 两个-在-一个-两个.
- 挑战传统单克隆抗体范式的抗体.
- 这种双重向抗体平台为涉及多个信号通路的疾病提供了新的治疗机会.
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