BRGSF-HIS mouse model | humanized for immune system

Applications of the BRGSF-HIS mouse model

The BRGSF-HIS mouse model can address a broad spectrum of therapeutic areas and applications, including bispecific antibodies, immuno-oncology, infectiology, vaccines, drug screening, and personalized medicine.

‍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

‍Application in efficacy assessment of:
- T-cell engagers
- Myeloid-targeted therapies aiming at reprogramming the TME
- Depleting agents working via ADCP and ADCC
- γδ T-cell expanders, as the model has shown to develop different subsets of γδ T cells

‍Application in safety assessment of:‍
- Anti-CD3 OKT3 antibody which targets the lymphoid and/or myeloid compartments, demonstrating the development of the hallmark features of cytokine release syndrome, as well as CRS-associated features induced by T-cell or myeloid targeting agents. The OKT3-induced CRS features could be alleviated by Infliximab
- Anti-VISTA pH-selective antibody, showing the safety of SNS-101 therapeutic antibody

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Validation

Effects of Flt3L-induced boost of myeloid compartment in BRGSF-HIS non-small-cell lung cancer (A549) tumor model
‍25-week-old BRGSF-HIS mice were injected with hFlt3L/Fc or vehicle prior to A549 inoculation (DO). Tumor growth was followed over 40 days (A), and tumors (400-500 mm) were collected and analyzed by flow cytometry. Percentage of human CD45⁺ cells was determined (B), and immune infiltrate composition was identified (C). T cells = hCD3⁺; NK cells= hCD37^-/hCD19^-/hCD56⁺; Myeloid cells = hCD3^-/hCD19^-/hCD56^-. B cells (hCD19⁺) were absent from the tumors. Data from 26 mice, 3 donors.
TNBC BRGSF-HIS model is donor-independent and recapitulates TNBC patients' TME
2-week-old BRGSF-HIS mice were injected with hFlt3L/Fc prior to MDA-MB-231 inoculation (DO). Tumor growth was followed over 30 days (A), and tumors (400-500m³) were collected and analyzed by flow cytometry. Percentage of human CD45⁺ cells in live cells (B), human monocytes in myeloid cells (C), hCD206⁺ M2 macrophages in monocytes (D), and hCD80⁺ and/or hCD86⁺ activated M2 macrophages (E) were determined. T cells = hCD3⁺/hCD56^-; NK cells = hCD3^-/hCD56⁺; Myeloid cells = hCD3^-/hCD56^-/hCD11b⁺/hCD33⁺; B cells = hCD19⁺/hCD3^-; Monocytes =hCD19^-/hCD3^-/hCD14⁺. Data from 25 mice, 5 donors.