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

• Published in: mAbs Vol. 8; no. 8; pp. 1525 - 1535
• Main Authors: Dashivets, Tetyana, Stracke, Jan, Dengl, Stefan, Knaupp, Alexander, Pollmann, Jan, Buchner, Johannes, Schlothauer, Tilman
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 16.11.2016
• Subjects: Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Antibody Affinity - immunology; Complementarity Determining Regions - chemistry; Complementarity Determining Regions - immunology; Humans; Oxidation-Reduction; Protein Processing, Post-Translational - immunology; Protein Stability; posttranslational modifications; target binding; oxidation; succinimide; Deamidation; monoclonal antibody; stability
• ISSN: 1942-0862; 1942-0870
• DOI: 10.1080/19420862.2016.1231277

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 V 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.