Monoclonal antibody-induced cytokine-release syndrome

Peter J Bugelski*a, Ram Achuthanandamb, Renold J Capocasalec, George Treacyd & Esther Bouman-Thioea Toxicology and Investigational Pharmacology, Centocor R&D, R-4-2, 145 King of Prussia Road, Radnor, PA 19087, USA and Department of Biomedical Engineering, Drexel University, Philadelphia, PA, USA. b Toxicology and Investigational Pharmacology, Centocor R&D, Radnor, PA, USA. c Toxicology and Investigational Pharmacology, Centocor R&D, Radnor, PA, USA. d Toxicology and Investigational Pharmacology and Translational Medicine, Centocor R&D, Radnor, PA, USA. e Translational Medicine, Centocor R&D, Radnor, PA, USA. † Author for correspondenceMonoclonal antibodies (mAbs) are widely used in anti-inflammatory and tumor therapy. Although effective, mAbs can cause a variety of adverse effects. An important toxicity seen with a few mAbs is cytokine-release syndrome (CRS). These mAbs include: alemtuzumab, muromonab-CD3, rituximab, tosituzumab, CP-870,893, LO-CD2a/BTI-322 and TGN1412. By contrast, over 30 mAbs used clinically are not associated with CRS. In this review, the clinical aspects of CRS, the mAbs associated with CRS, the cytokines involved and putative mechanisms mediating cytokine release will be discussed. This will be followed by a discussion of the poor predictive value of studies in animals and the prospects for creating in vitro screens. Finally, approaches to decreasing the probability of CRS, decreasing the severity or treating CRS, should it occur, will be described.