ImmunoSIGNAL™ Cytokine Storm

ImmunoSIGNAL™ Cytokine Storm Cellular Immunology Service

Cytokine storm, or cytokine release syndrome (CRS), is a potentially fatal immune reaction characterized by the massive release of proinflammatory cytokines. Cytokine storm has recently been associated with monoclonal antibody therapy. The events of the Phase 1 clinical trial of TGN1412, a CD28 superagonistic antibody, have highlighted the failure of preclinical models to predict toxicities and have stimulated new methods for assessing biologics prior to first-in-human testing. Ricerca Biosciences offers a robust in vitro assay to evaluate biologics for their potential to induce cytokine storm.

 

ImmunoSIGNAL™ Cytokine Storm assay

In this assay, compounds are evaluated for their ability to stimulate human peripheral blood mononuclear cells (PBMCs) to secrete specific cytokines and chemokines. Corresponding isotype controls are used to monitor non-specific activation of culture. Superagonistic anti-CD28 antibody is used as a positive control.

 

Compared with soluble antibody introduction, air-dry binding of antibodies produces dramatically higher induction of T cell cytokines, inflammatory cytokines and chemokines; therefore, study compounds are tested after air-dry binding to the test plate. Alternative antibody presentation methods (as wet bound or soluble) are available per customer request.

 

Service features

  • Cytokines measured: IFNγ, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12 p40, IL-17A, MIP1α, TNFα
  • Compounds are tested at 6 concentrations in duplicate
  • 10 cytokines and chemokines are measured and EC50, as well as fold induction, is reported
  • Superagonistic anti-CD28 antibody at 2 μg/well is used as a positive control, and isotype control is used as a negative control
  • Cell proliferation is measured by BrDU incorporation, and EC50 as well as fold induction is reported
  • One to 3 donor PBMCs can be selected by the client
  • Turnaround time is four weeks after the signed SOW and compounds are received
  • Minimum test article will depend on the top test concentration and the molecular weight