辐射触发的有效载荷释放提高了双特异性抗体的有效性
Victoria E Rodriguez-Castellanos1, Jeremy M Quintana2, Jose Manuel Martin2
1Massachusetts General Hospital, Boston, MA, United States.
Cancer research
|October 9, 2025
概括
辐射增强抗体-药物合物 (RAMP-ADCs) 提供向癌症治疗,仅在暴露于辐射时释放有效载荷. 这种创新方法提高了瘤向性,并最大限度地降低了系统性毒性,以改善治疗结果.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 生物结合化学 生物结合化学
背景情况:
- 治疗性抗体-药物合物 (ADC) 在癌症治疗中表现有前途,但面临着非目标效应和全身毒性挑战.
- 开发有针对性的药物输送系统对于提高癌症治疗的疗效和减少癌症治疗中不良事件至关重要.
研究的目的:
- 在暴露于电离辐射后,设计辐射放大抗体-药物合物 (RAMP-ADCs) 进行局部药物有效载荷释放.
- 为了增强瘤向性并最大限度地降低抗体与药物合物的全身毒性.
- 评估RAMP-ADCs使用具有不同有效载荷的双特异抗体amivantamab的疗效.
主要方法:
- 使用双特异抗体amivantamab开发RAMP-ADC,针对EGFR和MET受体.
- 有效载荷的结合 单甲基奥里斯丁E (MMAE) 或埃克萨特到RAMP-ADCs.
- 细胞毒性疗效和有效载荷传递选择性的体外评估.
- 在老鼠异种移植模型中RAMP-ADC疗效的体内评估.
主要成果:
- 拉姆普-ADCs在细胞毒性疗效上显示了多达2100倍的增强.
- 提高了瘤有效载荷传递选择性,高达760倍,系统毒性最小化.
- 与辐射相结合的RAMP-ADC治疗克服了细胞系的抗性,并在体内有效地阻断了瘤生长,延长了生存期.
结论:
- RAMP-ADCs为局部药物递送提供了一种新的策略,显著提高治疗效率和选择性.
- 这种辐射触发的激活机制提供了一种有希望的方法来克服传统ADCs的局限性.
- 在未来的癌症治疗中,RAMP-ADC平台具有与其他双特异性抗体开发的潜力.
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