预测对抗体药物合物的反应:专注于抗原的向性
Liliana Ascione1,2, Edoardo Crimini1,2, Dario Trapani1,2
1Division of Early Drug Development, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
The oncologist
|September 4, 2023
概括
抗体与药物联合体 (ADC) 是一种重要的癌症治疗方法. 这项研究探讨了目标抗原作为生物标志物,以预测ADC反应并指导患者选择以改善癌症治疗结果.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 生物标志物发现发现
背景情况:
- 抗体-药物合物 (ADC) 是关键的癌症治疗药物,通过向瘤细胞表面抗原,提供细胞毒性有效载荷.
- "旁观者"效应允许ADCs影响缺乏抗原表达的附近细胞.
- 从历史上看,ADC临床试验的纳入和批准需要特定的向抗原表达.
研究的目的:
- 研究抗原作为抗体-药物结合剂 (ADC) 疗效预测生物标记物的作用.
- 探索新的生物标志物,以指导ADC的使用和测序,特别是可用多个ADC.
- 根据表面表达或特定的遗传异常 (突变,过度表达) 来检查抗原向性.
主要方法:
- 审查已批准的ADC及其生物标志物的要求 (例如,ado-trastuzumab emtansine,fam-trastuzumab deruxtecan-nxki,mirvetuximab soravtansine-gynx).
- 在没有严格基于生物标志物的患者选择的情况下使用的ADCs的分析 (例如,sacituzumab govitecan).
- 讨论针对目标表达的新型评估方法,包括分子成像和体外测试.
主要成果:
- 虽然一些ADC需要特定抗原表达才能获得批准,但另一些ADC在没有这种限制的情况下在临床上使用.
- 目标抗原特征 (表面表达,突变,过度表达) 影响ADC的疗效和患者选择.
- 像分子成像等新兴技术为改善目标评估和患者分层提供了潜力.
结论:
- 识别和量化目标抗原对于优化ADC治疗和患者选择至关重要.
- 需要先进的评估方法来完善生物标志物分析,以获得更好的治疗结果.
- 强大的生物标志物对于在不断变化的ADC治疗环境中建立最佳治疗序列至关重要.
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