Current Regulatory Agency Recommendations Regarding Cytokine Storms
As a consequence of the lack of predictive power between pre-clinical and in-human results from the TGN1412 studies, a standard method to better predict cytokine storms was developed by the European Medicines Agency (EMA)2. The FDA also strongly recommends performing experiments to better predict cytokine storms3. At iQ Biosciences, we have developed expertise in better predicting cytokine storms by performing and optimizing cytokine bead assays (CBA) to assess the release of cytokines from human PBMCs in response to therapeutic molecules. Furthermore, our assays and methods are in concordance with EMA and FDA recommended guidelines, including the measurement of serum IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, and IFN-γ.
Please see our Cytokine Release Assay Workflow page describing our protocol and examples of data from our CRAs:
Mean serum concentration of IL-2, IL-4, IL-6, IL-10,
TNF-α, IFN-γ, and IL-17A from ‘Antibody X’ treated PBMCs.
In the competitive field of developing immune-modulatory therapeutics, or any antibody-based therapeutic for that matter, ensuring the molecule does not elicit a cytokine storm in first in-human trials is critical. In addition, with growth of companies specializing in biosimilars, as well as new technologies, such as bispecific (BiTE) or mulitmeric antibodies, these CRAs are just as important in providing pre-clinical data before in-human trials. Accordingly, the financial and, more importantly, patient health setbacks can have serious implications. With iQ Biosciences’ expertise in CBA to assess the expression of a variety of cytokines, drug developers can use our predictive assays to help assess the direction of their potential therapeutics and research programs.
How can iQ Biosciences help achieve your goals the smarter way?
- Suntharalingam, G. et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. The New England Journal of Medicine 355, 1018-1028 (2006).
- Stebbings, R., Eastwood, D., Poole, S. & Thorpe, R. After TGN1412: recent developments in cytokine release assays. Journal of Immunotoxicology 10, 75-82 (2013).
- Guidance for Industry Immunogenicity Assessment for Therapeutic Protein Products. FDA DRAFT GUIDANCE (Clinical/Medical, February 2013).