Presentation Description: There are a number of invitro assays used preclinically to predict the risk of immunogenicity, but the validation of these preclinical tools suffers from the relatively small number of accessible immunogenic molecules and the limited understanding of the mechanisms underlying the immunogenicity of biologics. Here, we present the post-hoc analysis of three monoclonal antibodies with high immunogenicity in clinic. Using a CD4 T cell proliferation assay, we were able to demonstrate that the three antibodies elicited a different CD4 T cell proliferative response with multiple donors in a PBMC assay but required different experimental conditions to induce these responses. These distinct capacities to promote CD4 T cell responses in vitro were mirrored by their different capacities to stimulate innate immune cells. These findings highlight the existence of distinct immune stimulatory mechanisms for immunogenic antibodies and have implications for the preclinical immunogenicity risk assessment of biologics.
Upon Completion, participant will be able to list the pertinent in vitro assays needed for the full assessment and interpretation of immunogenicity of therapeutic antibodies.
...interpret study data and will be able to conduct a thorough evaluation of antibodies, that do not have the same mechanism of action and how that impacts on immunogenicity.
...describe the tools and challenges for immunogenicity prediction during drug development and be able to see how preclinical immunogenicity can predictive of immunogenicity in humans.