The MHC Associated Peptide Proteomics Assay Is A Useful Tool For The Non-Clinical Assessment Of Immunogenicity

By Wojciech Jankowski, Christopher Kidchob, and Zuben E. Sauna, FDA and Campbell Bunce, Edward Cloake, and Ricardo Resende, Abzena

Originally published in Frontiers in Immunology. © 2023 Jankowski, Kidchob, Bunce, Cloake, Resende and Sauna.

Therapeutic protein immunogenicity poses a significant challenge in development and patient safety. Assessing this risk early is crucial. This study investigates MHC Associated Peptide Proteomics (MAPPS) as a comprehensive tool for immunogenicity evaluation in re-engineered Factor VIIa (FVIIa) variants.

Immunogenicity in protein drugs arises from anti-drug antibodies (ADAs), particularly neutralizing antibodies (NABs) that impact efficacy and safety. It necessitates early evaluation during development. Several tools and assays exist, targeting different stages of the immune response.

Most methods focus on predicting MHCII binding affinity or measuring T-cell responses, potentially overestimating or lacking epitope specificity. MAPPS uniquely identifies naturally presented peptides on MHC molecules, directly reflecting processing and presentation.

This study employed MAPPS to analyze immunogenic potential in FVIIa variants. Wild-type FVIIa, an immunogenic variant, and de-immunized analogs were compared. MAPPS results correlated with reduced T-cell responses of de-immunized variants, highlighting its potential for identifying clinically relevant epitopes and informing de-immunization strategies.

While more complex and resource-intensive, explore how MAPPS demonstrates promise as a valuable tool for comprehensive immunogenicity assessment in therapeutic protein development, contributing to safer and more effective biologics.