Abstract Traditional monoclonal antibodies and bispecifics have shown great promise for the treatment of various tumor entities. However, managing unwanted immunogenicity has become a challenge in the development of these promising therapeutics as there is a trend towards higher unwanted immune responses compared to classical monoclonal antibodies. Thorough assessment of their immunogenic potential is a crucial step in the development of safe biotherapeutics with high treatment efficacy. MHC-associated peptide proteomics (MAPPS Assay) enables the precise identification of all the regions of a protein that may evoke an immune response. High-sensitive MAPPS workflow in combination with high quality primary cells leads to higher numbers of identified self + non-self peptides and provides the analysis depth required for confident immunogenicity derisking and modulation. Here, we report the importance of peptides presented by HLA-DP and HLA-DQ (next to the standard HLA-DR presented peptides). Next, we also showed the first ever comparison of presented peptides by true immune cells: myeloid dendritic cells versus monocyte derived dendritic cells. Citation Format: Chloé Ackaert, Jana Schockaert, Aurélie Mazy, Christoph Schifflers, Martijn Vlaming, Elise Pepermans, Sofie Pattyn. MHC-associated peptide proteomics for immunogenicity risk assessment of immuno-oncology drug candidates abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 984.
Ackaert et al. (Fri,) studied this question.