Evaluation of cytokine storm risk during drug development

Craig Draper, PhD, Commercial & Marketing Manager, Eurofins Bioanalytical Services, CraigDraper@eurofins.com

Induction of cytokines, termed cytokine storm, is a common consequence of the administration of therapeutic antibodies. The most publicised occurrence was in 2006 when the administration of TGN1412 to subjects in a Phase I trial resulted in unprecedentedly high levels of cytokine release, leading to hospitalisation of the subjects with systemic organ failure. The subsequent focus on additional safety testing to prevent such tragic events has led the development of ex vivo assays capable of indicating whether a novel therapeutic antibody would present a significant risk for cytokine release. Such assays are critical safety evaluation tools in early stage drug candidate screening and are integral to the drug development process.

Eurofins has developed pre-qualified Cytokine Release Assays that encompass several of the key variables required for the cytokine release testing, including a modular choice of positive and negative controls (pavilizumab, trastuzumab, alemtuzumab, OKT3 and YTH12.5, as well as user-defined controls), and also solution, wet and dry coating presentations of compounds. Typical cytokines and chemokines tested are IFN-γ, IL-2, TNF-α, IL-10, IL-1β, IL-8 and IL-12p70. Additional markers can be added upon request.

The assays use heparinised whole blood, plasma depleted whole blood or isolated PBMC samples which are incubated with the investigational drug as well as with positive and negative controls. Plasma fractions are generated and then subjected to analysis on a choice of Luminex or Meso Scale Discovery platforms. Additionally, the treated blood samples can be subjected to analysis by flow cytometry for intracellular/surface marker analysis. For very early stage safety evaluations, Eurofins also offers cytokine release assays using specific cell lines.

The Cytokine Release Assays from Eurofins provide drug developers with rapid access to early drug safety data, and as core assays are pre-qualified, development costs and time are eliminated.

For more information, visit: www.eurofins.com/bioanalyticalservices.com