A valuable means of testing the immune modulating potential of a biopharmaceutical product is to assess its ability to stimulate cytokine production by immune cells. By profiling the type and quantity of cytokines induced in vitro using Cytokine Screen™, a picture can be established of whether the product induces an immune response. Depending on the anticipated mode of action of the product, an immune response could be unwanted or favourable.
Cytokine Screen™ – Cytokine Release Syndrome Assay
Biopharmaceutical products can potentially activate innate and adaptive immune cells resulting in rapid and excessive cytokine release which can lead to cytokine release syndrome (CRS), sometimes referred to as cytokine storm. Elevated serum cytokine concentrations are measurable in patients within minutes to hours of infusion of the product. A cytokine storm can result in significant and potentially life-threatening toxicity and patients feel very unwell. It has been observed following administration of alemtuzumab and basiliximab, amongst others, and came to particular prominence during the Phase I clinical testing of TGN1412. The dramatic and unexpected effects of TGN1412 highlighted the limitation of preclinical models to identify the risk of a product inducing a cytokine storm.
GreenLight’s enhanced in vitro assay, Cytokine Screen™, evaluates the risk of biopharmaceutical products causing a cytokine storm. The assay can identify the risk prior to it being progressed into clinical development.
About the assay
GreenLight’s Cytokine Screen™ – Cytokine Release Assay uses fresh whole human blood within 4 hours of blood draw, providing close proximity to the state of circulating cells in vivo. The high sensitivity of cytokine detection in the assay allows measurement of changes in multiple cytokines, such as IL-6, IL-8, IL-10, IFN-γ and TNF-α., in parallel.
Multiple therapeutic antibodies known to be associated with cytokine release-mediated clinical toxicity have been used to correlate the relative severity of the cytokine response induced by the test products. The assay combines the quantity, type, and number of cytokines induced with the frequency of donor responses to create a composite picture of the relative risk of test compounds to induce a cytokine storm.
The data indicates that alemtuzumab induces a significant increase in the frequency and concentration of cytokines released compared to centuximab, which is consistent with the published literature on the occurrence of cytokine response syndrome in patients for these two antibodies.
These profiles are part of a broader data set analysing cytokine responses from a number of therapeutic products with a known risk of inducing a cytokine storm. The figure below summarises IL-6 responses measured in the assay when test sample were used at 0.1-100 μg/mL.
Working with GreenLight
GreenLight’s services are tailored to each project to ensure that the objectives are met or exceeded. Experienced project teams are assigned to each study focusing on progressing projects through to results. Our clients widely regard us as professional and attentive partners who deliver quality results.
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