EpiScreen™ Immunogenicity Testing
EpiScreen™ is a highly accurate and sensitive human ex vivo T cell assay technology used to determine helper CD4+ T cell responses to whole proteins, peptides, formulations and NCEs (New Chemical Entities). Proprietary steps in the technology include liquid nitrogen storage of pre-processed HLA-typed peripheral blood mononuclear cells (PBMCs) which are depleted of CD8+ T cells, and that retain sensitivity, as well as assay to assay reproducibility typically observed using fresh (non-frozen) PBMC samples. A typical study uses PBMCs from a minimum of 50 donors which are carefully selected to provide a distribution of HLA-DR allotypes that are matched (coverage and frequency of HLA alleles) against the human population relevant to the study. For all EpiScreen™ assay formats an analysis of potential association between MHC class II haplotypes and CD4+ T cell responses is performed.
Ex vivo T cell assay analysis of a number of therapeutic proteins that have progressed to the clinic and for which clinical immunogenicity data has been published, reveals a strong correlation between T cell activation in the EpiScreen™ assay and the development of anti-therapeutic antibody responses in patients. Based on this benchmark data, EpiScreen™ is widely used for preclinical analysis of whole therapeutic proteins in order to assess the potential for immunogenicity in the clinic.
Comparative analysis of a range of proteins with clinical immunogenicity data also shows a strong relationship between the presence and potency of T cell epitopes with the immunogenicity of the corresponding protein.