Corticosteroids Discovery for Cytokine Release Syndrome (CRS) Management

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Creative Biolabs is a contract research organisation (CRO) that provides drug discovery and development solutions using its world-renowned expertise in drug discovery, immunology, and cancer therapy. Founded in New York in 2007, Creative Biolabs operates in state-of-the-art facilities to provide superior quality data to support your drug discovery program.

Cytokine Release Syndrome

Cytokine release syndrome (CRS) is a form of systemic inflammatory response syndrome which occurs in some diseases or infections. CRS is also an adverse effect of immunotherapies, including monoclonal antibody drugs, T cell therapy (see Fig.1). If the CRS is severe, the CRS will be called cytokine storms which will cause high fever, hypotension, hypoxia, occasionally seizures and cerebral oedema, etc. which are harmful to patients. Along with the wide application of immunotherapies in clinical cases, it becomes necessary to explore more treatment approaches to control the toxicities caused by immunotherapies. With well-known immunosuppressive functions, corticosteroids are used following the infusion of CAR-T cell therapy in clinical cases when the toxicities are refractory to cytokine targeting therapies.

Fig.1 Symptoms of CRS. (Riegler, 2019)

Corticosteroids Discovery for CRS Management

Currently, the standard interventions to control CRS include 10 mg dexamethasone intravenous every 6 hours and 1mg/kg methylprednisolone intravenous every 12 hours. It has been demonstrated that low dose and short regimen of corticosteroids do not impair the proliferation or cytotoxicity of CAR-T cells. Taken together, corticosteroids are valuable approaches to treat CRS. To support the successful application of innovative cancer immunotherapies, it's vital to manage the CRS to maintain under the safe range. Hence, Creative Biolabs launched a series of solutions to offer a broad range of drug discovery and development services to manage the CRS. Here we offer discovery and development services for corticosteroids drugs which are effective to manage moderate-to-severe CRS.

Fig.2 Management of chimeric antigen receptor (CAR) T-cell toxicity. (Bonifant, 2016)

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References

Khadka, Roman H., et al. "Management of cytokine release syndrome: an update on emerging antigen-specific T cell engaging immunotherapies." Immunotherapy 11.10 (2019): 851-857.
Riegler, Lara L., Gavin P. Jones, and Daniel W. Lee. "Current approaches in the grading and management of cytokine release syndrome after chimeric antigen receptor T-cell therapy." Therapeutics and clinical risk management 15 (2019): 323.
Bonifant, Challice L., et al. "Toxicity and management in CAR T-cell therapy." Molecular Therapy-Oncolytics 3 (2016): 16011.