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通过因丁介导蛋白质跨拼接反应构建IgG-Fab2双特异抗体

Risa Yamada¹, Ishin Nakahara², Izumi Kumagai²

¹Graduate School of Science and Engineering, Yamagata University, 4-3-16 Jyonan, Yonezawa, Yamagata, 992-8510, Japan.

Scientific reports

|September 25, 2023

概括

这项研究引入了一种使用蛋白质结合制造双特异抗体 (bsAbs) 的新方法,克服了常见的生产挑战. 工程IgG-Fab2 bsAbs显示有效的标结合和T细胞介导的细胞毒性.

科学领域:

生物技术是生物技术.
免疫学免疫学免疫学
蛋白质工程是指蛋白质工程.

背景情况:

双特异性抗体 (bsAbs) 通过同时向多个抗原来提供治疗潜力.
错误的重链和轻链配对是bsAb生产的一个重大障碍,导致效率和产量下降.
现有的bsAb生产方法面临着结构相似性的挑战,导致错误配对的链.

研究的目的:

为了展示一种新的bsAb构造方法,使用interin介导的蛋白质转接.
创建IgG-Fab2类型的bsAbs,一种改性抗体结构,具有增强的抗原结合能力.
为了规避bsAb生产中固有的链接配对问题.

主要方法:

工程双特异抗体 (bsAb) 构造使用因特因介导蛋白质转接.
单独表达和净化IgG和Fab组件,以避免连锁配对问题.
优化蛋白质结合通过删除潜在的糖化残留来提高产量和减少副作用.

主要成果:

成功地产生IgG-Fab2型bsAbs,特别针对Her2/CD3.
证明了工程 bsAbs. 的目标结合活性.
确认T细胞介导的细胞毒性,表明功能疗效.

结论:

通过蛋白质介导的蛋白质转接提供了一种有效的策略,用于产生IgG-Fab2类型的bsAbs.
开发的方法成功地克服了bsAb生产中的链接配对问题.
这种方法扩大了可用于强大的bsAb制造的方法目录.

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