一个自组装的蛋白质平台,用于多价值人造抗体和抗体-药物结合物的插入-运行定制
Yuzhe Chen1, Yunchuan Huang1, Shisheng Wang1,2
1Division of Liver Surgery and NHC Key Lab of Transplant Engineering and Immunology, Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Angewandte Chemie (International ed. in English)
|August 25, 2025
概括
我们开发了一种多功能蛋白质平台, 这种系统可以模块化组装多价药物,增强标结合,优化药物输送以提高疗效.
科学领域:
- 生物技术
- 蛋白质工程
- 药物开发
背景情况:
- 在控制药物动力学和药理学特性方面,模块化组装具有挑战性.
- 开发用于先进药物设计的多功能平台对于下一代疗法至关重要.
研究的目的:
- 为了介绍ATPlug,一个自我组装的蛋白质平台,用于模块化构建多价值治疗.
- 展示该平台在制造人工抗体和抗体药物联合体 (ADC) 的能力.
主要方法:
- 设计了一个整合三元化,SpyCatcher和蛋白结合域的蛋白质平台.
- 组装的多价值结构针对EGFR,PD-L1和VEGF.
- 针对EGFR过度表达的瘤开发并测试了基于ATPlug的ADC.
主要成果:
- 目标结合能力提高了30倍.
- 通过阿尔伯明的提车延长血半衰期.
- ATPlug-ADCs对EGFR具有1. 8nM的结合亲和力,并具有强大的瘤抑制作用.
结论:
- ATPlug为下一代疗法提供了一个"插即用"的策略.
- 该平台可以实现定制的多价值和多药协同效应.
- 在制造强效和选择性抗体-药物结合物方面已被证明是成功的.
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