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Updated: Mar 15, 2026

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
Published on: May 4, 2017
Oxidation in the complementarity-determining regions differentially influences the properties of therapeutic
Tetyana Dashivets1,2, Jan Stracke3, Stefan Dengl1
1a Roche Pharma Research and Early Development (pRED), Large Molecule Research, Roche Innovation Center Munich , Germany.
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.
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