Cytokine release syndrome (CRS)

Chasing the storm: Enhanced translatability in BRGSF-HIS preclinical model

BRGSF-HIS:

• BRGSF is the most immunodeficient mouse model to date
• Reconstituted BRGSF-HIS mice harbor all the major human hematopoietic cell subsets from the lymphoid and myeloid compartments

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BRGSF-HIS is a useful tool for safety assessment of therapeutic biologics.

Immune-related adverse events are a major concern when developing immunotherapies, calling for relevant and efficient preclinical models to predict and study compounds’ toxicity before transitioning to the clinical stages. Cytokine release syndrome (CRS) is a systemic inflammatory response that can lead to multiorgan failure and thus, be fatal. Immunodeficient mice with a reconstituted human immune system (HIS) have recently been described as useful preclinical models for toxicity and adverse event studies. genOway’s BRGSF-HIS model represents the versatile tool for toxicity studies of immunotherapies.

Data obtained from studies performed jointly with CRO partners show that the efficient reconstitution of the myeloid compartment in BRGSF-HIS mice allows the notable detection of human cytokines such as hIL-2, hIL-6, hTNF-α and hIFN-γ in OKT3-treated BRGSF-HIS mice. Finally, these induced BRGSF-HIS mice also displayed body weight loss and temperature drop. Importantly, these inflammatory symptoms were mitigated by tocilizumab, (anti-human IL-6 R), a widely accepted treatment of first choice in severe CRS in humans.