ADC药物配体结合生物分析常见技术问题探讨

摘要/Abstract

摘要： [摘要] 目的：抗体药物偶联物（ADC）是一类新的生物治疗药物，通常由细胞毒性有效载荷通过连接子与抗体共价结合组成。ADC在体内经历不断的脱偶联和生物转化过程，导致形成复杂且结构不均一的混合物，除了脱偶联的游离抗体和游离载荷外，还存在不同程度与小分子药物偶联的ADC分子，因此，对生物分析方法的开发带来很大挑战。为了解ADC药物在非临床和临床研发阶段的药代和药效特征，以及免疫原性和安全性，对给药后体内存在的不同分子形式的实体比如药物偶联的抗体、裸抗和总抗体等需要使用不同的方法进行分析。本文总结了在ADC药物分析方法开发中遇到的较为常见的技术问题并提供相关的解决方案，以期为相关的分析方法开发提供参考，促进ADC药物安全有效地开发。

关键词: font-size:medium, ">抗体偶联药物；配体结合分析；药代；抗药抗体；生物分析

Abstract: Antibody-drug conjugates (ADCs) are a new class of biotherapeutics consisting of cytotoxic payloads covalently bound to antibodies via linkers. ADCs undergo continuous deconjugation and biotransformation processes in vivo， resulting in the formation of a complex and heterogeneous mixture. In addition to free antibody and free payload， there are also ADC molecules that are conjugated to small molecule drugs to varying degrees， which pose a great challenge to the development of bioanalytical assays. In order to understand the pharmacokinetic and pharmacodynamic characteristics， as well as immunogenicity and safety of ADC drugs in the non-clinical and clinical development phases， different analytical assays are required to analyze the different molecular forms of entities present in vivo after administration， such as drug-conjugated antibody， naked antibody， and total antibody. This paper summarizes the technical issues commonly encountered in the development of analytical assays for ADC drugs in our laboratory in recent years， and offers relevant solutions， thereby providing peers with references for the development of analytical assays and facilitating the development of safe and effective ADC drugs.

Key words: font-size:medium, ">Antibody-drug conjugate； Ligand binding assay； Pharmacokinetics； Anti-drug antibody； Bioanalysis

中图分类号:

秦秋平, 陶亦敏, 刘婷婷, 闫莉萍, 宫丽崑. ADC药物配体结合生物分析常见技术问题探讨[J]. 中国药物评价, 2023, 40(4): 281-288.

QIN Qiu-ping, TAO Yi-min, LIU Ting-ting, YAN Li-ping, GONG Li-kun. Technical Issues Commonly Encountered in Ligand Binding Assays for Bioanalysis of ADC Drugs[J]. CHINESE JOURNAL OF DRUG EVALUATION, 2023, 40(4): 281-288.

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