Sr Scientist Merck & Co Inc West Point, Pennsylvania
Presentation Description: Monoclonal antibodies (mAbs) can undergo a variety of post-translational modifications with some of the most well-known being oxidation and deamidation. These modifications can impact the efficacy and stability of mAbs. However, the potential for these modifications to cause anti-mAb immune responses is unknown. We compared stir stressed and unstressed forms of a therapeutic mAb, trastuzumab, for differences in antigen presentation of mAb-derived peptides via an MHC class II associated peptide proteomics (MAPPs) assay. We found that stress treatment resulted in an increased the signal intensity of mAb-derived peptides after normalization. Furthermore, differences were observed in the signal intensities of deamidated and oxidized peptides. Presentation of these modified peptides have the potential to initiate anti-mAb immune responses, which are the subject of future investigations.
Understand the impact of deamidation and oxidation on antigen presentation of therapeutic proteins
incorporate post translational modifications into immunogenicity risk assessment of biologics
conduct analysis of the impact of post translation modifications on antigen presentation with MHC class II associated peptide proteomics data