MHC II MAPPs for High-Confident Immunogenicity Risk Assessment of Biotherapeutics

Area of Science:

• Biopharmaceutical development
• Immunology
• Proteomics

Background:

• Biotherapeutics can elicit immunogenicity, impacting drug safety and efficacy.
• Assessing immunogenicity involves understanding protein processing by antigen-presenting cells (APCs) and peptide presentation via MHC class II (HLA class II).
• Current methods may not fully capture the in vivo processing and presentation landscape.

Purpose of the Study:

• To describe a robust protocol for MHC II-associated peptide proteomics (MAPPs) assay.
• To enable identification of therapeutic protein-derived peptides presented by individual MHC II variants.
• To enhance immunogenicity risk assessment for biotherapeutics.

Main Methods:

• Development and validation of a highly robust protocol for MHC II MAPPs.
• Utilizing MAPPs to analyze peptides derived from therapeutic proteins.
• Characterizing peptide-MHC II complexes relevant to immune responses.

Main Results:

• The described protocol provides a reliable method for MHC II MAPPs.
• The assay identifies specific peptides from therapeutic proteins bound to MHC II molecules.
• This offers insights into the processing and presentation steps relevant to immunogenicity.

Conclusions:

• The robust MHC II MAPPs protocol is a valuable tool for biopharmaceutical development.
• This assay aids in predicting and understanding T cell responses to biotherapeutics.
• Improved immunogenicity assessment contributes to safer and more effective drug development.