成功的抗体药物偶联物的管道拓展的关键指标。
Key metrics to expanding the pipeline of successful antibody-drug conjugates.
机构信息
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
出版信息
Trends Pharmacol Sci. 2021 Oct;42(10):803-812. doi: 10.1016/j.tips.2021.07.005. Epub 2021 Aug 26.
Although the recent FDA approval of six new antibody-drug conjugates (ADCs) is promising, attrition of ADCs during clinical development remains high. The inherent complexity of ADCs is a double-edged sword that provides opportunities for perfecting therapeutic action while also increasing confounding factors in therapeutic failures. ADC design drives their pharmacokinetics and pharmacodynamics, and requires deeper analysis than the commonly used C and area under the curve (AUC) metrics to scale dosing to the clinic. Common features of current FDA-approved ADCs targeting solid tumors include humanized IgG1 antibody domains, highly expressed tumor receptors, and large antibody doses. The potential consequences of these shared features for clinical pharmacokinetics and mechanism of action are discussed, and key design aspects for successful solid tumor ADCs are highlighted.
尽管最近 FDA 批准了六种新的抗体药物偶联物 (ADC)，但 ADC 在临床开发过程中的损耗仍然很高。ADC 的固有复杂性是一把双刃剑，它为完善治疗作用提供了机会，同时也增加了治疗失败的混杂因素。ADC 的设计决定了其药代动力学和药效学，需要比常用的 C 和曲线下面积 (AUC) 指标进行更深入的分析，以将剂量扩展到临床应用。目前针对实体瘤的 FDA 批准的 ADC 的共同特点包括人源化 IgG1 抗体结构域、高度表达的肿瘤受体和大剂量抗体。讨论了这些共同特征对临床药代动力学和作用机制的潜在影响，并强调了成功的实体瘤 ADC 的关键设计方面。
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