吴白杨, 王凌, 姜静. 模型引导的药物开发在抗体偶联药物领域的应用J. 药学学报, 2025, 60(2): 288-299. DOI: 10.16438/j.0513-4870.2024-0787
引用本文: 吴白杨, 王凌, 姜静. 模型引导的药物开发在抗体偶联药物领域的应用J. 药学学报, 2025, 60(2): 288-299. DOI: 10.16438/j.0513-4870.2024-0787
WU Bai-yang, WANG Ling, JIANG Jing. Application of model informed drug development in the field of antibody drug conjugatesJ. Acta Pharmaceutica Sinica, 2025, 60(2): 288-299. DOI: 10.16438/j.0513-4870.2024-0787
Citation: WU Bai-yang, WANG Ling, JIANG Jing. Application of model informed drug development in the field of antibody drug conjugatesJ. Acta Pharmaceutica Sinica, 2025, 60(2): 288-299. DOI: 10.16438/j.0513-4870.2024-0787

模型引导的药物开发在抗体偶联药物领域的应用

Application of model informed drug development in the field of antibody drug conjugates

  • 摘要: 抗体偶联药物(antibody drug conjugates, ADC) 作为抗肿瘤治疗的前沿技术, 近年来取得了显著进展。ADC通过连接子将高活性小分子毒素与高特异性抗体进行偶联, 不仅能够实现对肿瘤细胞的精准打击, 同时降低了药物的全身毒性, 进而扩大了治疗的有效性和安全性窗口。然而, 由于ADC分子设计的复杂性, 其疗效和安全性受多种因素影响。模型引导的药物开发(model informed drug development, MIDD) 是一种通过数学和统计模型进行建模和模拟, 对药物研发进行定量分析和决策指导的方法。这种方法为新药研发提供强大的工具支持。通过MIDD整合ADC相关的多方面数据和信息, 有助于理解ADC的复杂机制、药代动力学和药效学等作用特征, 为优化ADC研发流程和临床转化决策提供独特见解。本文将介绍MIDD和ADC的基本概念, 并浅析MIDD在ADC研发不同阶段的应用案例, 旨在为ADC的发展提供有益参考。

     

    Abstract: Antibody drug conjugates (ADC) have emerged as a cutting-edge technology in anti-tumor treatment, making significant strides in recent years. ADC couple a highly active small molecule toxin payload to highly specific antibodies through a linker, enabling precise targeting of tumor cells while reducing systemic toxicity, thereby expanding the therapeutic window. However, due to the complexity of ADC molecule design, its efficacy and safety are influenced by various factors. Model-informed drug development (MIDD) is a powerful tool that utilizes various mathematical models for modeling and simulation to conduct quantitative analysis, guiding drug development and decision-making. By integrating multi-faceted data and information using mathematical models, it is possible to gain insights into the complex mechanisms, pharmacokinetics, and pharmacodynamics of ADC, providing unique perspectives for optimizing ADC development processes and clinical translation decisions. This review will introduce the basic concepts of MIDD and ADC and discuss application cases of MIDD in different stages of ADC development, aiming to provide beneficial references for the advancement of ADC.

     

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