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Cytokine. 2016 Sep;85:101-8. doi: 10.1016/j.cyto.2016.06.006. Epub 2016 Jun 13.

Cytokine release: A workshop proceedings on the state-of-the-science, current challenges and future directions.

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Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA.
Pfizer Inc., 1 Eastern Point Road, Groton, CT 06340, USA.
Amgen, Inc., Comparative Biology and Safety Sciences, USA.
Envigo, Woolley Road, Alconbury, Huntingdon, Cambridgeshire PE28 4HS, United Kingdom.
US Food and Drug Administration, 10903 New Hampshire Ave, Rockville, MD, USA.
Imperial College London, London SW3 6LY, United Kingdom.
ILSI Health and Environmental Sciences Institute, 1156 15th St NW, Suite 200, Washington, DC 20005, USA.
ILSI Health and Environmental Sciences Institute, 1156 15th St NW, Suite 200, Washington, DC 20005, USA. Electronic address:
Charles River Laboratories, 20222 Transcanadien, Senneville, QC H9X 3R3, Canada.
Paul-Ehrlich-Institute, Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich Str. 51-59, 63225 Langen, Germany.
Medimmune, Inc., One MedImmune Way, Gaithersburg, MD 20878, USA.
The National Institute of Biological Standards and Controls, Blanche Ln, South Mimms, Potters Bar EN6 3QG, United Kingdom.
Johnson and Johnson, Inc., 1 Johnson and Johnson Plaza, New Brunswick, NJ 08933, USA.


In October 2013, the International Life Sciences Institute - Health and Environmental Sciences Institute Immunotoxicology Technical Committee (ILSI-HESI ITC) held a one-day workshop entitled, "Workshop on Cytokine Release: State-of-the-Science, Current Challenges and Future Directions". The workshop brought together scientists from pharmaceutical, academic, health authority, and contract research organizations to discuss novel approaches and current challenges for the use of in vitro cytokine release assays (CRAs) for the identification of cytokine release syndrome (CRS) potential of novel monoclonal antibody (mAb) therapeutics. Topics presented encompassed a regulatory perspective on cytokine release and assessment, case studies regarding the translatability of preclinical cytokine data to the clinic, and the latest state of the science of CRAs, including comparisons between mAb therapeutics within one platform and across several assay platforms, a novel physiological assay platform, and assay optimization approaches such as determination of FcR expression profiles and use of statistical tests. The data and approaches presented confirmed that multiple CRA platforms are in use for identification of CRS potential and that the choice of a particular CRA platform is highly dependent on the availability of resources for individual laboratories (e.g. positive and negative controls, number of human blood donors), the assay through-put required, and the mechanism-of-action of the therapeutic candidate to be tested. Workshop participants agreed that more data on the predictive performance of CRA platforms is needed, and current efforts to compare in vitro assay results with clinical cytokine assessments were discussed. In summary, many laboratories continue to focus research efforts on the improvement of the translatability of current CRA platforms as well explore novel approaches which may lead to more accurate, and potentially patient-specific, CRS prediction in the future.


Cytokine release assay; Cytokine release syndrome; Pro-inflammatory cytokines

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