a Analytical and Formulation Development , Agensys, Inc., an affiliate of Astellas, Inc , Santa Monica , CA , USA.
b Department of Biochemistry and Molecular Biology , University of Miami Miller School of Medicine , Miami , FL , USA.
MAbs. 2018 Nov-Dec;10(8):1190-1199. doi: 10.1080/19420862.2018.1521128. Epub 2018 Oct 19.
Antibody-drug conjugates (ADCs) that are formed using thiol-maleimide chemistry are commonly produced by reactions that occur at or above neutral pHs. Alkaline environments can promote disulfide bond scrambling, and may result in the reconfiguration of interchain disulfide bonds in IgG antibodies, particularly in the IgG2 and IgG4 subclasses. IgG2-A and IgG2-B antibodies generated under basic conditions yielded ADCs with comparable average drug-to-antibody ratios and conjugate distributions. In contrast, the antibody disulfide configuration affected the distribution of ADCs generated under acidic conditions. The similarities of the ADCs derived from alkaline reactions were attributed to the scrambling of interchain disulfide bonds during the partial reduction step, where conversion of the IgG2-A isoform to the IgG2-B isoform was favored.
抗体药物偶联物（ADCs）是通过使用巯基-马来酰亚胺化学形成的，通常是在中性或以上 pH 值条件下发生反应生产的。碱性环境可以促进二硫键重排，并且可能导致 IgG 抗体的链间二硫键重新配置，特别是在 IgG2 和 IgG4 亚类中。在碱性条件下产生的 IgG2-A 和 IgG2-B 抗体生成的 ADC 具有可比的平均药物抗体比和偶联物分布。相比之下，在酸性条件下生成的 ADC 的抗体二硫键构型会影响其分布。碱性反应生成的 ADC 的相似性归因于部分还原步骤中链间二硫键的重排，其中 IgG2-A 异构体向 IgG2-B 异构体的转化更有利。
