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设计 HER2 向的双类抗体,以促进受体内化,恢复抗瘤功效

Xinlin Liu^1,2,3, Wanpeng Yu³, Yihuan Wang^2,3

¹Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.

Frontiers in immunology

|November 24, 2025

概括

针对HER2的新双类抗体克服了对当前疗法的耐药性. 这些工程抗体促进受体内部化,并在耐药细胞中表现出增强的抗瘤活性.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
生物技术是生物技术.

背景情况:

人体表皮生长因子受体2 (HER2) 是各种癌症的关键驱动因素.
针对HER2的治疗方法,如trastuzumab和pertuzumab,可以改善治疗结果,但也面临抗药性挑战.

研究的目的:

设计针对HER2的新型双类抗体 (bpAbs).
为了评估这些bpAbs对抗逆祖马布抗性癌细胞的疗效.

主要方法:

设计了两种IgG-VHH双型抗体 (bpAbs) 结合HER2细胞外域 (ECD) 结合纳米体.
评估了bpAbs向非重叠的HER2表位素的能力,促进受体内化,并抑制瘤生长.
利用结构建模来理解HER2-bpAbs的相互作用.

主要成果:

设计的bpAbs,A9B5-Bs-5和A9B5-Bs-7在耐药细胞中显示出相比trastuzumab/pertuzumab组合更高的抗瘤活性.
bpAbs诱导了HER2受体的快速内化,并通过跨结合模式发挥作用.
结构建模表明受体聚类和干扰联体驱动的HER2异构化.

结论:

皮导向的双型抗体设计增强了HER2下调.
这一策略可以恢复耐药瘤对HER2向治疗的敏感性.
这些发现支持下一代HER2向生物制剂的开发.

关键词:

在HER2中,HER2是HER2.两种类型的抗体.纳米体是一个纳米体.没有重叠的表观.对于特拉斯图祖马布的耐药性

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