Our BRGSF-HIS mouse model, the only CD34+ reconstituted model with functional human lymphoid and myeloid compartments without side effects, can be used in a wide range of applications, whether you're exploring new therapeutic targets, evaluating drug efficacy, or performing safety assessment, and can help you significantly accelerate your path to clinical trials.
Latest insights
Application in safety assessment of:
- Anti-CD3 antibody OKT3 targeting the lymphoid and/or myeloid compartments (Myeloid and dendritic cells enhance therapeutics-induced cytokine release syndrome features in humanized BRGSF-HIS preclinical model) showing:
- Development of CRS hallmark features, revealing the key contribution of myeloid cell compartment in the system
- CRS-associated features triggered by T cell or myeloid-targeting compounds
- Infliximab alleviates OKT3-induced CRS features
- Anti-VISTA pH-selective antibody (VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response):
- SNS-101 is safe and does not induce CRS, contrary to OKT3
- Safety assessment was key to the approval of the IND application filed by Sensei Bio for their SNS-101 anti-VISTA antibody in June 2023 (BRGSF-HIS and hVISTA Knock-in as preclinical models for immunotherapies).
Application in tumor biology:
- Assessment of myeloid and lymphoid human cells recruitment and activation profile into the tumor microenvironment (TME) shaped by tumor cell type and tumor burden, using tumor engraftments MDA-MB-231 and HPAFII (see genOway's poster 'Tumor cell line-derived xenograft subtype shapes tumor microenvironment composition in BRGSF-HIS mice using tumor engraftments', presented at AACR 2024)
Applications in efficacy assessment of:
- T-cell engagers (see genOway's poster 'Myeloid cells' contribution is key in CRS pathophysiology induced by T-cell engagers in BRGSF-HIS model', presented at AACR 2023)
- Myeloid-targeted therapies aiming at reprogramming the TME (see Macomics' poster 'Discovery of MACO355: a first in mechanism ligand-blocking independent LILRB1/2/3 antibody for cancer therapy', presented at AACR 2024)
- Depleting agents working via ADCP and ADCC (see publication 'Improved in vitro and in vivo activity againstCD303-expressing targets of the chimeric 122A2 antibody selected for specific glycosylation pattern' by Fournier et al.)
- γδ T-cell expanders, as the model has shown to develop different subsets of γδ T cells (see Figure)
What makes the BRGSF-HIS model special?
- Human immune system reconstituted using human CD34+ has functional human lymphoid cells, such as B cells, T cells, NK cells, and functional human myeloid cells, including conventional dendritic cells, plasmacytoid cells and monocytes/macrophages
- Highly permissive to human xenograft, including primary or established tumor cells (CDX or PDXs)
- Assessment of compounds with wide therapeutic window made possible by:
- Long-lasting engraftment of human lymphoid and myeloid compartments
- Long lifespan, similar to that of a WT mouse, and no side effect or body weight loss associated with human immune system development
BRGSF-HIS: latest insights
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