- This is an example of an HLA-transgenic mouse response to a protein therapeutic.
Basic animal models such as in-bred mice, guinea pigs, and even primate models fall short when used to assess the potential of protein based therapeutics to induce immune responses in human beings. The proteins that make up MHC molecules, the dominant mediators of adaptive immune response, are among the most highly variable in the human genome. That variability is common to all mammals. Animal models simply do not present the same T cell epitope repertoire as humans. HLA mice, mice engineered to present fully human MHC haplotypes, are the only effective pre-clinical model of human immune response. At EpiVax we have assembled a panel of HLA knock out/knock in transgenic mice and a set of robust protocols for assessing immune response in those models. Mouse strains containing the human HLA molecules DRB1*0301 and DRB1*0401 are currently available. Several other strains of mice will soon be in production. We believe these mice represent the best available proxy for studying the immunogenic potential of your molecule in humans.
EpiVax employs a competition-based HLA binding assay initially described by Kwok et al. and adapted for high throughput by EpiVax. This assay employs highly purified Class II molecules for which we have an exclusive worldwide license. This assay format is far superior in sensitivity and specificity compared to cell-based assay formats. Non-linear regression analysis is performed and an IC50 value is calculated. Binding assays are typically performed for four alleles: DRB1*0101, DRB1*0301, DRB1*0701, DRB1*1501 with DRB1*0801 and DRB1*1301 available upon request.
