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Cell Based Phenotypic >> Immunology >> Cytokine storm

Cytokine release syndrome

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Cytokine storm is an acute immune response initiated by a positive feedback loop between pro-inflammatory cytokines and immune cells.  The symptoms of a cytokine storm range from swelling to high fever and nausea and, if the response is unchecked, the result can be multi-organ failure or death.  Naturally occurring viruses are a common culprit behind cytokine storms.  However, it has become evident that large molecule therapeutics (e.g., vaccines, therapeutic mAbs and other biologics) pose the same risk.

Assessing the risk of large molecules for the potential of acute or prolonged immunogenicity is a regulatory requirement.  In their 2013 "Immunogenicity Assessment for Therapeutic Protein Products" guidance, the FDA has recommended in vitro assessment of immunological response in either human whole blood or peripheral blood mononuclear cells.  This proactive, early-stage evaluation of cellular activation, proliferation and cytokine release may help reduce the risk of adverse reactions in later clinical development.

We can help provide this crucial early stage immunogenic assessment by testing your large molecule biologic against our bank of human donor PBMC using a combination of cell proliferation and multiplexed cytokine/chemokine release assays. 

Advantage of ImmunoSignal™ cytokine storm assays:

  • Developed according to FDA recommendations for preclinical testing of biologics
  • Reliable, well-characterized and responsive bank of human cells from genetic diverse donors
  • Measurement of 10 cytokines/chemokines
    • IL-10, IL-1β, IL-12p40, IL-17A, IFNγ, IL-2, IL-6, IL-8, MIP-1α & TNFα
  • Lymphocyte proliferation measured by BrdU incorporation
  • Appropriate controls
    • Positive controls / reference compounds - anti-CD28 SA, anti-CD3 (OKT3) or anti-CD3 (UCHT1)
    • Negative controls - corresponding isotype antibodies for positive controls are included, isotype for test compound (optional)
  • Experience with cytokine storm assay services since 2012
  • Flexible testing conditions:
    • Choice of human PBMC donor, availability of non-human primate PBMCs
    • Compound presentation - air dry, wet bound or soluble
    • Induction time frame - 24 or 48h



Figure 1. Anti-CD28 SA stimulation of pre-incubated human PBMC increases lymphocyte proliferation

Proliferation of PBMC pre-incubated for 24h in response to 48h stimulation by air-dried (red), wet bound (blue) or soluble (green) anti-CD28 SA antibodies.