Applying the appropriate assay format for cytokine release assays to deliver the appropriate interpretation of safety risks

抄録

Following the serious adverse events that resulted in severe cytokine storm responses in individuals dosed with TGN1412, it has been important to perform in-vitro toxicology tests on any compound that has the potential to modulate immune activation status to predict the potential for activation of a cytokine release mechanisms. Over the last 10 years many investigators have assessed a variety of in-vitro cellular assays for evaluation of this response but these do not always reflect the true biologic mechanisms taking place. This poster will review data generated for liquid phase, solid phase, and co-culture assay formats with positive controls (Anti-CD3 Monoclonal antibody, Anti-CD28 Monoclonal antibody, Anti-Her2 Monoclonal antibody and CD19&CD3 bi-specific T-cell engager) which are known to have different modes of action for induction of cytokine release. This data will be used to highlight the importance of choosing an appropriate assay format for characterisation of cytokine release. It will discuss how target biology considerations and test article structural considerations need to be considered for choosing the appropriate cytokine release assay format. Details of how the Fc region of a monoclonal antibody will govern the choice for a solid phase format and how co-culture systems with PBMCs and endothelial cells can be used for a greater physiological understanding will be presented. Utilising these data the poster will show how applying the appropriate assay format can be used to accurately predict the potential for cytokine storm for novel biologics.