Oxidation in the complementarity-determining regions differentially influences the properties of therapeutic antibodies

Tetyana Dashivets, Jan Stracke, Stefan Dengl, Alexander Knaupp, Jan Pollmann, Johannes Buchner, Tilman Schlothauer

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Therapeutic antibodies can undergo a variety of chemical modification reactions in vitro. Depending on the site of modification, either antigen binding or Fc-mediated functions can be affected. Oxidation of tryptophan residues is one of the post-translational modifications leading to altered antibody functionality. In this study, we examined the structural and functional properties of a therapeutic antibody construct and 2 affinity matured variants thereof. Two of the 3 antibodies carry an oxidation-prone tryptophan residue in the complementarity-determining region of the VL domain. We demonstrate the differences in the stability and bioactivity of the 3 antibodies, and reveal differential degradation pathways for the antibodies susceptible to oxidation.

Original languageEnglish
Pages (from-to)1525-1535
Number of pages11
JournalmAbs
Volume8
Issue number8
DOIs
StatePublished - 16 Nov 2016

Keywords

  • Deamidation
  • monoclonal antibody
  • oxidation
  • posttranslational modifications
  • stability
  • succinimide
  • target binding

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