Oxidation in the complementarity-determining regions differentially influences the properties of therapeutic antibodies. Issue 8 (16th November 2016)

• Record Type: Journal Article
• Authors: Dashivets, Tetyana; Stracke, Jan; Dengl, Stefan; Knaupp, Alexander; Pollmann, Jan; Buchner, Johannes; Schlothauer, Tilman
• Is Part Of: MAbs. Volume 8:Issue 8(2016)
• Page Start: 1525
• Page End: 1535
• Publication Date: 2016-11-16
• Subjects: Deamidation -- monoclonal antibody -- oxidation -- posttranslational modifications -- succinimide -- stability -- target binding; Monoclonal antibodies -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Periodicals; Antibodies, Monoclonal -- Periodicals; 616.0798
• DOI: 10.1080/19420862.2016.1231277
• Languages: English
• ISSNs: 1942-0862

Abstract

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.