Cytokine release syndrome
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:
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.