Abstract
Cytokine release syndrome (CRS), which is caused by excessive cytokine release, is known as a side effect of antibody drugs. Symptoms of CRS include fever and headache, but in severe cases, tachycardia, hypotension, and dyspnea may appear. A well-known example is an anti-CD28 superagonist antibody TGN1412, which induced a multiple organ failure in all subjects of the clinical trial in 2006. The side effects of TGN1412 were not observed in toxicity studies in monkeys, and later it became clear that species differences were involved. After this tragedy, various in vitro CRAs using human blood cells have been investigated to detect cytokine release by antibody drugs. However, an in vitro CRA method with high clinical predictability has not been established even 18 years after the TGN1412 incident. This is due to a different characteristics of each method, multiple mechanisms of CRS, and diversity of the formats and mode of action (MoA) of antibody drugs.
Currently, considering the characteristics of each method, we are conducting our research with the following two objectives:
1) To establish an assay method that dose not overlook the cytokine release potential of antibody drugs.
2) To make a strategy for selecting an appropriate assay method considering the MoA of antibody drugs.
In this presentation, we will introduce the results of several existing in vitro CRAs and our newly developed in vitro CRAs using some antibody drugs, including TGN1412. We hope that our presentation will provide a good opportunity to think about the strategy for selecting assay methods.
