Module 9 2024

03/09/2024

Immunogenicity Prediction

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

Tools/platforms used during discovery/early development. Role in lead selection, humanisation/deimmunisation, sequence optimisation, 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 • Future: Engineered tissues, Organoids models ???

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Preclinical Immunogenicity

Immunogenicity in animals is typically not predictive of immunogenicity in humans

‘…the predictivity of animal studies for evaluation of immunogenicity in humans is considered low. 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

‘… animal studies are generally limited in their ability to predict the incidence of human immune responses to a therapeutic protein product, but they may be useful in describing the consequences of antibody responses’ Guidance for Industry, Immunogenicity Assessment for Therapeutic Protein Products, FDA, 2014

Assessment of immunogenicity in animals is primarily for interpretation of toxicology and pharmacology data.

The Organisation for Professionals in Regulatory Affairs

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