Module 9 2021

22/03/2021

Immunogenicity prediction

Difficult to predict • the incidence of unwanted immunogenicity • the characteristics of the elicited immune responses • the clinical consequences & significance of such immunogenicity

Tools/platforms used during discovery/early development. Role in lead selection, humanisation/deimmunisation, process changes

• In silico tools: epitope databases & computer algorithms to map T-cell and/or B-cell epitopes and assess HLA-peptide binding • In vitro HLA binding assays: peptide - HLA cl II binding and affinity • In vitro T cell assays: T cells activation, proliferation • In vitro Antigen-presenting cells (APC) assays e.g., dendritic cells maturation • In vitro processing assay e.g., MAPPs (MHC Associated Peptide Proteomics) • Animal models: humanised mouse models, non-human primates

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Preclinical immunogenicity

Immunogenicity in animals is typically not predictive of immunogenicity in humans. Assessment of immunogenicity in animals is primarily for interpretation of toxicology and pharmacology data. ‘’Non-clinical in vitro or in vivo studies aiming at predicting immunogenicity in humans are normally not required’’ Guideline on Immunogenicity Assessment of Therapeutic Proteins, EMEA/CHMP/BMWP/14327/2006 Rev.1, 2017

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