This study investigates the role of myeloid and dendritic cells in the development of cytokine release syndrome (CRS) induced by immunotherapies. Using humanized BRGSF mice reconstituted with human umbilical cord blood CD34+ cells (BRGSF-CBC), the research evaluates the contribution of these cells to CRS and assesses the model's relevance for preclinical testing of CRS-managing therapies.
Injection of the anti-CD3 antibody OKT3 in BRGSF-CBC mice induced hallmark features of CRS, including inflammatory cytokine release, alterations in immune cell distribution and activation, body weight loss, and temperature drop. Boosting myeloid and dendritic cells with human Flt3L enhanced these CRS features, highlighting the significant role of these cells in CRS development. Treatment with the clinical CRS-managing therapy Infliximab efficiently attenuated OKT3-induced toxicity.
The BRGSF mouse model was developed by genOway. These mice are reconstituted with human CD34+ hematopoietic stem cells, leading to the development of a human-like immune system, including myeloid and dendritic cell populations.
Cytokine release syndrome, Immunotherapy, Myeloid cells, Dendritic cells, Humanized mouse model
Humanized mouse model, BRGSF mice, CD34+ cell reconstitution, Cytokine release assessment, Preclinical immunotherapy testing
From model design to experimental results
Tailor-made solutions adapted to scientific questions
Comprehensive dataset package
Generated with biopharma partners and in-house
Scientific follow-up and advice along the project
Collaborative approach for problem solving and development of innovative models
Breeding facilities in US and Europe
Certified health status from professional breeders
