具有恒定区域融合架构的工程双功能抗体
Juanjuan Du1,2, Yu Cao2, Yan Liu1
1California Institute for Biomedical Research , 11119 N. Torrey Pines Road, La Jolla, California 92037, United States.
Journal of the American Chemical Society
|November 30, 2017
概括
研究人员开发了一种新方法,通过将蛋白质插入抗体结构中来制造双功能抗体. 这种方法产生了强大的Her2 × CD3双特异抗体,具有显著的癌症治疗潜力.
科学领域:
- 免疫学
- 生物技术
- 蛋白质工程
背景情况:
- 抗体工程对于开发向疗法至关重要.
- 目前制造多功能抗体的方法存在局限性.
- 需要多功能抗体平台用于各种治疗应用.
研究的目的:
- 开发一种通过蛋白质移植产生双功能抗体的新方法.
- 描述工程抗体的体外和体外疗效.
- 为了证明Her2 × CD3双特异抗体的治疗潜力.
主要方法:
- 将全长蛋白植入抗体或抗原结合碎片 (Fabs) 的常态区域循环中.
- 通过将抗Her2单链可变片段 (ScFv) 插入抗CD3 Fab中,构建一个Her2 × CD3双特异性抗体 (BsAb).
- 在体外评估细胞活动,生化特性和稳定性.
- 在老鼠异种移植模型中评估体内抗瘤活性.
主要成果:
- 工程双功能抗体表现出卓越的体外活性,稳定性和生理化学性质.
- 在亚皮科莫拉度下,Her2 × CD3 BsAb显示有效的向细胞溶解.
- 在表达Her2的异种移植模型中,Her2 × CD3 BsAb在体内显示出强大的抗瘤功效.
- 蛋白质插入方法成功地产生了多功能抗体.
结论:
- 将蛋白质移植到抗体常数区域循环中是产生双功能抗体的可行策略.
- 人工合成的多功能抗体在癌症治疗中具有显著的治疗潜力.
- 这种方法为开发基于抗体的新疗法提供了多功能平台.
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