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在基于exatecan的抗体与药物结合物的可切割连接剂的生物评估:对DXd和exo-linker平台的比较研究

Tomohiro Watanabe^1,2, Yusuke Iwai¹, Natsuki Shikida¹

¹Ajinomoto Co., Inc., 1-1, Suzuki-Cho, Kawasaki-Ku, Kawasaki-Shi, Kanagawa 210-8681, Japan.

|September 8, 2025

概括

一个新的链接平台增强了抗体-药物合物 (ADC) 稳定性和药理动力学. 这种新的ADC技术显示了比现有治疗方法更好的特性,为下一代癌症治疗提供了潜在的潜力.

科学领域:

在瘤学瘤学.
制药科学制药科学
生物结合化学生物结合化学

背景情况:

抗体-药物合物 (ADC) 是向癌症治疗的重要类别.
在ADC中,传统的可切割链接剂可能会带来稳定性和药理动力学的挑战.
需要先进的链接器技术来提高ADC的性能.

研究的目的:

开发和评估一种针对抗体-药物联合体 (ADC) 的新型链接平台.
为了评估ADC的稳定性,药理动力学和疗效,利用这个新的链接器.
为了将新型ADC与临床验证的ADCtrastuzumab-deruxtecan (T-DXd) 进行比较.

主要方法:

开发一种用于ADC构建的新型链接平台.
通过使用新型链接剂,与外EVC-Exatecan (APL-1082) 结合trastuzumab.
在老鼠模型中评估体内疗效和药物动力学概况.
与特拉斯图祖马布-德鲁克斯坦 (T-DXd) 的比较.
使用AJICAP特定位点的结合技术,用于高药对抗体比 (DAR) 的ADCs.

主要成果:

新型ADC (APL-1082) 呈现出卓越的稳定性,并保持了药物对抗体比率 (DAR).
与T-DXd相比,观察到减少聚合和疏水性,这表明药理动力学有所改善.
使用APL-1082和AJICAP生产了具有同质性和有利的物理化学性质的高DARADCs (DAR10).
新型链接器平台展示了增强的ADC特性.

结论:

新的链接平台为ADCs提供了增强的稳定性和药理动力学特征.
这项技术有可能克服传统可切割连接器的局限性.
开发的链接器是一个多功能平台,用于创建下一代ADC,提高疗效和治疗潜力.

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