Evidence of disulfide bond scrambling during production of an antibody-drug conjugate

Lily Pei Yao Liu-Shin, Adam Fung, Arun Malhotra, Gayathri Ratnaswamy

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1190-1199
Number of pages10
JournalmAbs
Volume10
Issue number8
DOIs
StatePublished - Nov 17 2018

Keywords

  • ADC
  • antibody-drug conjugate
  • conjugation process
  • conjugation profile
  • disulfide isoform
  • disulfide scrambling
  • IgG2
  • mAb
  • monoclonal antibody

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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