Cytokine Release Syndrome, or Cytokine Storm, is one of the major causes of multiple-organ failure and mortality in COVID-19 and other viral or pathogenic infections, or in severe sepsis and inflammation following trauma or major surgery. As recent events have shown, large molecule therapeutics including vaccines, monoclonal antibodies, and other biologics present the same risk.
Our Cytokine Storm Assay has been used by clients since 2012 because of its value in assessing the efficacy and immune safety of both small molecule anti-inflammatory therapies and biologics, including CAR-T therapies for oncology. Benefits include:
- Anti-inflammatory Efficacy
The Cytokine Storm acute immune response following SARS-CoV-2 infection results from a positive feedback loop between pro-inflammatory cytokines and immune cells. This can lead to acute respiratory distress syndrome (ARDS), multi-organ failure, and mortalities of some COVID-19 patients. - Biologics Immune Safety
Assess the risk of therapeutic protein and cell products for acute or prolonged immunogenicity potential in response to regulatory recommendations in the US and EU of both the Food and Drug Administration (FDA) and European Medicines Agency (EMA). One recommended assay is preclinical in vitro evaluation of cytokine release with peripheral blood mononuclear cells (PBMCs). Testing whole blood is also possible.
Eurofins Discovery Cytokine Storm Assay Overview
Figure 1. Mechanism model of cytokine release data describing cytokine storm induction. A. Superagonist, therapeutic mAb TGN1412 binds cell surface receptors CD28 or variant CD28 and simultaneously FcɣRI on vascular endothelial cells, promoting rapid release of multiple proinflammatory cytokines from monocytes (mono), natural killer (NK), and T cells. Subsequent exponential release of cytokines leads to endothelial cell damage, loss of capillary integrity, and multiple organ failure. B. Immobilized superagonist anti-CD28 mAb (clone ANC28.1/5D10) stimulates robust induction of pro-inflammatory cytokines in human PBMCs. Induction levels of each cytokine were interpolated from a standard curve using 5-point non-linear regression analysis.
- Determine immune safety of test agents or candidates slated for repurposing
- Obtain dose-response data on lead candidates compared to reference standards
- Appropriate for small molecules, biologics, nucleic acid therapeutic candidates including aptamers and nutraceuticals
- Maximize efforts with custom assay modifications, induction pathways, and biomarker readouts
Developed according to FDA recommendations for preclinical testing of biologics, our Cytokine Storm Assay satisfies recommendations from regulatory agencies to assess the risk of large molecules to induce acute or prolonged immunogenicity.
Early evaluation of immune cell activation, T cell proliferation, and cytokine release is a proactive step you can take to help reduce the risk of adverse reactions in clinical development. Evaluate your preclinical candidates or screen a large pool of test agents against our bank of human donor PBMCs using a combination of cell proliferation, cytotoxicity, and multiplexed cytokine & chemokine readouts.
Go further with our suite of validated assays and physiological models that enable the discovery and development of efficacious and safe therapeutics with improved chance of clinical success.
