BRGSF-HIS mice as a predictive tool for safety assessment of biologics
BRGSF-HIS for safety assessment
Background
Immunotherapies are efficacious but are often associated to immune-related adverse events, such as cytokine release syndrome (CRS). Safety assessment of therapeutics in preclinical models remains challenging, as they should be relevant and translational. Models exhibiting a human immune system are widely used, but the composition of the human immune system developed remains a concern. Here we report the use of BRGSF mice, an immunodeficient mouse model which can be reconstituted with human cord blood CD34+ cells (BRGSF-CD34+) or PBMC (BRGSF-PBMC). BRGSF-CD34+ develop functional human lymphoid and myeloid compartments, with systematic and persistent presence of plasmacytoid dendritic cells (pDCs), conventional dendritic cells (cDCs), and monocytes/macrophages. Their myeloid and dendritic compartments can be transiently boosted with exogenous human Flt3L injections. In contrary to other models which overexpress human cytokines to develop human myeloid cells, Flt3L-treated BRGSF-CD34+ mice do not show side effects.
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