Cytokine release: A workshop proceedings on the state-of-the-science, current challenges and future directions.
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.
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA.
Christine
C
Grimaldi
Pfizer Inc., 1 Eastern Point Road, Groton, CT 06340, USA.
Deborah
D
Finco
Amgen, Inc., Comparative Biology and Safety Sciences, USA.
Madeline M
MM
Fort
Envigo, Woolley Road, Alconbury, Huntingdon, Cambridgeshire PE28 4HS, United Kingdom.
Daniel
D
Gliddon
Envigo, Woolley Road, Alconbury, Huntingdon, Cambridgeshire PE28 4HS, United Kingdom.
Kirsty
K
Harper
US Food and Drug Administration, 10903 New Hampshire Ave, Rockville, MD, USA.
Whitney S
WS
Helms
Imperial College London, London SW3 6LY, United Kingdom.
Jane A
JA
Mitchell
ILSI Health and Environmental Sciences Institute, 1156 15th St NW, Suite 200, Washington, DC 20005, USA.
Raegan
R
O'Lone
ILSI Health and Environmental Sciences Institute, 1156 15th St NW, Suite 200, Washington, DC 20005, USA. Electronic address: sparish@hesiglobal.org.
Stanley T
ST
Parish
Charles River Laboratories, 20222 Transcanadien, Senneville, QC H9X 3R3, Canada.
Marie-Soleil
MS
Piche
Imperial College London, London SW3 6LY, United Kingdom.
Daniel M
DM
Reed
Paul-Ehrlich-Institute, Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich Str. 51-59, 63225 Langen, Germany.
Gabriele
G
Reichmann
Medimmune, Inc., One MedImmune Way, Gaithersburg, MD 20878, USA.
Patricia C
PC
Ryan
The National Institute of Biological Standards and Controls, Blanche Ln, South Mimms, Potters Bar EN6 3QG, United Kingdom.
Richard
R
Stebbings
Johnson and Johnson, Inc., 1 Johnson and Johnson Plaza, New Brunswick, NJ 08933, USA.
Mindi
M
Walker
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D001681:Biological Assay / Q000379:methods; D016207:Cytokines / Q000097:blood*; D006801:Humans; D007154:Immune System Diseases / Q000097:blood / Q000188:drug therapy
D000911:Antibodies, Monoclonal; D016207:Cytokines
Cytokine release assay; Cytokine release syndrome; Pro-inflammatory cytokines