Scientists from the National Institute of Biological Standards and control have developed the first antibody reference panel for the qualification and validation of cytokine release assay platforms. The panel (NIBSC code: 19/156), which is now available from our product catalogue, will help to assure the safety of novel biotherapeutics.
Therapies such as monoclonal antibodies (mAbs) that are designed to the target the immune system carry the risk of inducing undesired immune reactions. In extreme cases, they can trigger cytokine release syndrome (CRS) – a rapid inflammatory response caused by the secretion of pro-inflammatory cytokines from white blood cells. To minimise this risk, novel mAbs are evaluated using in vitro cytokine release assays as part of their routine preclinical safety assessments. Until now, however, the lack of available standards for positive and negative control antibodies made the qualification of cytokine release assays difficult.
The NIBSC reference panel contains three positive controls of lyophilised recombinant mAbs known to induce CRS in the clinic: human anti-CD52, mouse anti-CD3 and human superagonistic anti-CD28 mAbs. These cover different mechanisms of action and induce the release of cytokines from different cell types. The panel also includes three isotype-matched negative controls.
An international collaborative study involving eleven laboratories was carried out in order to evaluate the performance of the reference panel. The results of the study, published in the journal Cytokine X, confirmed the expected behaviour of the controls with the positive controls inducing cytokine release across a variety of cytokine release assay platforms.
Dr Sandrine Vessillier, who led the collaborative study, comments:
“The use of this common set of positive and negative control monoclonal antibodies will provide information on the reproducibility, robustness and potential limitations of a CRA platform. It will establish confidence in the ability of any novel CRA to identify potential CRS risk ahead of first-in-human clinical trials.”
Find out more about the work of our immunotoxicology group.
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