Antibody-Drug Conjugates (ADCs) consist of antibodies attached to cytotoxic small molecules or biological agents (i.e., payloads) through chemical linkers which may be cleavable or non-cleavable. The development of new ADCs is challenging, particularly the process of attaching the linker-payload construct to the antibody (i.e., the conjugation process). One of the major problems associated with conjugation is high hydrophobicity of the payload which can lead to low yields of the ADC through aggregation and/or lower than desired Drug-Antibody Ratios (DARs). We report here a UPLC-based assay that can be used to study the physicochemical properties of ADC payloads at an early stage of development, and to provide information on whether the hydrophilic-hydrophobic balance is suitable for conjugation or further physicochemical optimization is required. The assay is relatively simple to establish and should be of use to those working in the ADC area.

中文翻译：

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基于UPLC的测定法，用于评估抗体-药物偶联物（ADC）有效载荷的疏水性。

抗体-药物偶联物（ADC）由通过可裂解或不可裂解的化学接头与细胞毒性小分子或生物制剂（即有效载荷）连接的抗体组成。新ADC的开发具有挑战性，特别是将连接子有效载荷构建体连接至抗体的过程（即缀合过程）。与共轭相关的主要问题之一是有效载荷的高疏水性，这可能导致聚集而导致ADC的产量低和/或低于所需的药物-抗体比率（DARs）。我们在这里报告基于UPLC的分析方法，该方法可用于研究ADC负载在开发的早期阶段的理化性质，并提供有关亲水-疏水平衡是否适合共轭或需要进一步理化优化的信息。