Predicting cytokine storms: it's about density.

摘要

CRS is a common clinical event with antibody therapies such as rituximab and anti-CD3 antibody. After the infusion of the CD28 superagonist TGN1412 all 6 healthy recipients unexpectedly suffered a severe form of CRS, often referred to as a cytokine storm.2 The massive release of proinflam-matory cytokines rapidly progressed to severe multiorgan failure requiring advanced medical resuscitation. The events of the March 2006 first-in-human trial of TGN1412 have since sparked a fundamental discussion regarding the failure of preclini-cal models to predict toxicities and how new biologies are assessed before first-in-human testing (see figure).