目标表位的单氨基酸变体可以对基于抗体的疗法产生抗性
Romina Marone1,2, Erblin Asllanaj3,4, Giuseppina Capoferri1,2
1Department of Biomedicine, University Hospital Basel and University of Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.
Science translational medicine
|December 17, 2025
概括
自然遗传变异可以减少或消除治疗单克隆抗体 (mAbs) 的有效性. 这影响了治疗结果,并强调了在抗体治疗中需要考虑患者的遗传多样性.
科学领域:
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
- 遗传学 遗传学 是一个
背景情况:
- 单克隆抗体 (mAbs) 在瘤学和免疫学中提供向治疗.
- 由于目标表位的微小变化,mAbs的高特异性可能会受到损害.
研究的目的:
- 研究自然单核酸变异如何影响治疗性单克隆抗体 (mAbs) 的抗原识别.
- 评估基因变异对基于抗体的治疗疗效的临床影响.
主要方法:
- 对已批准和正在研究的mAbs.的抗体-抗原接口中的蛋白质变异的分析.
- 使用工程细胞系 (例如,HER-2变异) 对抗体结合和细胞杀死变异影响的实验验证.
主要成果:
- 对于大多数研究的mAbs,在抗体-抗原接口附近确定了变异.
- 在特定变异 (例如,HER-2 P594H) 的病例中观察到抗体结合和治疗抵抗的完全丧失.
- 证明自然变异可以赋予抗体疗法,包括抗体与药物合物的初级耐药性.
结论:
- 自然遗传变异可能导致对单克隆抗体疗法的初级耐药性.
- 遗传多样性影响治疗结果和患者管理.
- 考虑到人群特异性遗传变异对于抗体药物开发和临床决策至关重要.
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