人性化双抗激素抗体的合理设计
Yong Zhang1, Yan Liu, Ying Wang
1California Institute for Biomedical Research (Calibr) , 11119 North Torrey Pines Road, La Jolla, California 92037, United States.
Journal of the American Chemical Society
|December 11, 2014
概括
研究人员设计了一种新的"茎"抗体结构,以制造人类抗体激动剂. 这种多功能CDR融合策略成功生成了具有强大治疗作用的功能双功能抗体融合蛋白.
科学领域:
- 抗体工程是一种抗体工程.
- 蛋白质工程是一种蛋白质工程.
- 免疫学 免疫学 免疫学
背景情况:
- 牛抗体BLV1H12具有具有独特的"茎旋"图案的超长CDR3H.
- 这种动机允许用细胞因子和生长因子取代"旋"域,以产生激进抗体.
研究的目的:
- 为了将牛的"茎"架构转化为人性化的抗体,以产生人类抗体激动剂.
- 开发一种多功能CDR融合策略,用于创建基于抗体的多功能疗法.
主要方法:
- 在人性化的抗体trastuzumab (Herceptin) 中设计了"茎"架构.
- 融合的人类红色素 (hEPO) 或颗粒细胞殖民地刺激因子 (hGCSF) 进入赫塞丁的各种CDR循环 (CDR3H,CDR2H,CDR3L).
- 通过将hEPO和hGCSF接种到重链和轻链CDR3循环中,分别生成了一个双功能融合蛋白.
主要成果:
- 在哺乳动物细胞中表达的融合蛋白具有良好的产量.
- 融合蛋白的体外生物活动与原生hEPO和hGCSF相当.
- 这种双功能抗体融合蛋白显示出强大的EPO和GCSF激动剂活性.
结论:
- 该CDR-融合策略是多功能,用于生成功能的人类抗体仿真体.
- 这种方法为开发基于多功能抗体的治疗方法提供了一种新的方法.
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