文章：

整合体外分析以优化抗体-药物偶联物候选物筛选

Integrating In Vitro Analytics for Improved Antibody–Drug Conjugate Candidate Selection

原文发布日期：3 January 2026

DOI: 10.3390/cancers18010164

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: The development of antibody–drug conjugates (ADCs) presents significant scientific and operational challenges, from optimising conjugation chemistry and linker stability to establishing robust analytical controls. Advanced analytical methods, particularly the combination of plasma stability assays with enzymatic studies, are essential for early screening and characterisation of ADC candidates. Integrating these in vitro assays with powerful data analysis software accelerates structure–activity relationship assessments and the identification of stable compounds in plasma. Methods: This article examines how combined analytical and computational approaches enhance candidate selection by offering valuable insights into the metabolic fate and stability risks of ADCs. Results: Our research shows correlation between in vitro stability profiles and in vivo pharmacokinetic (PK) data, demonstrating the predictive power of early-stage analytical studies. Implementation of software-driven visualisation and analysis enables faster, data-informed decision making, streamlining the triage process to prioritise candidates with optimal PK and pharmacodynamics (PD) characteristics. Conclusions: These findings highlight the critical need for integrated in vitro analytics and computational tools in efficient ADC development, supporting the selection of candidates with the greatest potential for clinical success and facilitating a more effective and accelerated path from discovery to clinical application.

摘要翻译： 

**背景/目的：** 抗体偶联药物的开发面临着从优化偶联化学与连接子稳定性，到建立稳健的分析控制方法等一系列重大的科学与操作挑战。先进的分析方法，特别是血浆稳定性测定与酶解研究的结合，对于ADC候选药物的早期筛选与表征至关重要。将这些体外测定方法与强大的数据分析软件相结合，可加速构效关系评估及血浆中稳定化合物的鉴定。 **方法：** 本文探讨了如何通过结合分析与计算手段，为深入理解ADC的代谢归宿与稳定性风险提供宝贵见解，从而优化候选药物的筛选。 **结果：** 我们的研究表明，体外稳定性特征与体内药代动力学数据之间存在相关性，这证明了早期分析研究的预测能力。实施软件驱动的可视化与分析，能够实现更快速、基于数据的决策，简化筛选流程，从而优先选择具有最佳PK和药效学特性的候选药物。 **结论：** 这些发现凸显了在高效的ADC开发过程中，整合体外分析与计算工具的迫切需求。这有助于筛选出最具临床成功潜力的候选药物，并支持一条从发现到临床应用更有效、更快速的路径。

原文链接：

Integrating In Vitro Analytics for Improved Antibody–Drug Conjugate Candidate Selection