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温度促进了Pembrolizumab中的Fab臂交换

Mohammad Karbalaeimahdi¹, Puneet K Singh¹, Razvan C Stan¹

¹Department of Basic Medical Science, Chonnam National University, Hwasun 58128, Republic of Korea.

International journal of biological macromolecules

|August 6, 2025

概括

较高的温度改变了Pembrolizumab (一种IgG4抗体) 的结构,促进了Fab-arm交换并减少了抗原结合. 这影响了其治疗疗效和免疫相互作用的潜力.

科学领域:

免疫学免疫学免疫学
生物化学生物化学
蛋白质工程是指蛋白质工程.

背景情况:

免疫球蛋白G4 (IgG4) 抗体是能够进行Fab域交换的动态分子.
这一过程在特定的体外条件下产生双特异性抗体,其抗炎活性降低.

研究的目的:

为了研究生理和非生理温度对免疫治疗IgG4抗体Pembrolizumab分子内部重组的影响.
了解温度如何影响Pembrolizumab的结构动态和抗原结合特性.

主要方法:

在不同温度 (25°C,37°C,38.5°C和40°C) 下对 pembrolizumab 的结构和功能的比较分析.
评估与Fab-arm交换相关的形状变化.
测量抗体-抗原与编程死亡-1 (PD-1) 受体的结合亲和力.

主要成果:

与较低温度 (25°C和37°C) 相比,布罗利祖马布在高温 (38.5°C和40°C) 时经历了支持Fab-arm交换的形状变化.
较高的温度导致布罗利祖马布与其目标,即编程死亡-1受体的结合亲和力降低.
高温促进Fc域与Fc/补充受体的结合,并减少在目标上的停留时间.

结论:

温度对Pembrolizumab的结构完整性和功能活性产生重大影响.
虽然受温度影响,但Fab-arm交换并没有被正规的S228P突变废除.
在较高温度下观察到的结合亲和力和Fc受体相互作用的变化对Pembrolizumab的治疗用途有影响.

关键词:

在Fab-Arm交易所.分子动力学分子动力学在PD-1中使用PD-1.这就是Pembrolizumab.表面等离子体共振是什么?温度的温度的温度的温度的温度.

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