Title of Challenge Improving the predictive capacity of in vitro cytokine release assays to reduce animal use and drug attrition Background

Cytokines are soluble signalling molecules which are released by cells of the immune system in response to antigen binding. Large molecule therapeutics such as antibodies can also trigger cytokine release and immune cell activation either directly by their V regions or by Fc regions binding to Fc receptors. A severe example of this was seen in the trial of TGN1412, an anti-CD28 IgG4, which activated T-cells resulting in massive cytokine generation and severe pathology in the volunteers that received it (1, 2).