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Fast and Accurate Evaluation of Oxidation‐Induced Destabilization of mAbs
Author(s) -
Piatti Patricia,
Mohamadi Mariam,
Tschammer Nuška,
Breitsprecher Dennis,
Fung Peter A.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.800.9
Subject(s) - trastuzumab , monoclonal antibody , binding affinities , chemistry , computational biology , folding (dsp implementation) , cancer research , antibody , pharmacology , breast cancer , biochemistry , cancer , biology , medicine , receptor , immunology , electrical engineering , engineering
The applicability of monoclonal antibodies (mAbs) in therapeutic research continues to rise — they now account for almost 50% of protein‐based drugs. Monitoring their quality as well as binding properties are critical as these parameters provide insight into mAb functionality and efficacy as potential drugs. Here we study trastuzumab, a monoclonal antibody that has been used to successfully treat patients with certain forms of breast cancer. Trastuzumab acts by binding to and interfering with the HER2/neu receptor in cancer patients. Using two complementary technologies, we examine how targeted oxidation affects trastuzumab structure and therefore its binding capabilities to protein A. First, a rapid analysis of oxidation‐induced changes in mAb folding and stability was performed. The same samples were then analyzed to determine how oxidation compromises mAb interactions. Oxidational stress directly correlated with weaker binding affinities of the Fc region towards protein A, showcasing fast and accurate characterization of trastuzumab sample quality. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .