BRGSF-HIS Mouse Model

Immunodeficient mouse

The BRGSF-HIS mouse possesses the most functional reconstituted human immune system currently available on the market. Indeed, this mouse, based on the cutting edge BRGSF model, offers new opportunities to address human-specific questions in a more relevant manner, facilitating translational research in several biomedical disciplines and approaches.

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Applications – Translatability to patient

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.

infographic brgsf-his applications

BRGSF-HIS features

The BRGSF-HIS mouse model possesses all of the major human hematopoietic cell subsets, such as B cells, T cells (including CD4⁺ Treg cells), NK cells, and the myeloid compartment, including dendritic cells (DCs), plasmacytoid cells (pDCs), and monocytes/macrophages.

Highly permissive to human xenograft, including primary or established tumor cells (CDX or PDXs) by virtue of the SIRPα^NOD allele expression
Lifespan after humanization similar to that of the wild-type mouse _⇨ supports long-term engraftment studies
Robustness to traveling (stable immune system)
Suitable to assess the effects of radiation treatment in vivo due to the absence of the SCID mutation on a BALB/c background
A complete, functional complement system makes this a powerful tool for complement-dependent cytotoxicity (CDC) studies

Strategy for the generation of the BRGSF-HIS mouse

References for model validation

Model validation

Labarthe L, Henriquez S, Lambotte O, Di Santo JP, Le Grand R, Pflumio F, Arcangeli ML, Legrand N, Bourgeois C. Frontline Science: Exhaustion and senescence marker profiles on human T cells in BRGSF-A2 humanized mice resemble those in human samples. J Leukoc Biol. 2019 Aug 4.

Lopez-Lastra S, Masse-Ranson G, Fiquet O, Darche S, Serafini N, Li Y, Dusséaux M, Strick-Marchand H, Di Santo JP. A functional DC cross talk promotes human ILC homeostasis in humanized mice. Blood Adv. 2017 Apr 6.

Strick-Marchand H, Dusséaux M, Darche S, Huntington ND, Legrand N, Masse-Ranson G, Corcuff E, Ahodantin J, Weijer K, Spits H, Kremsdorf D, Di Santo JP. A novel mouse model for stable engraftment of a human immune system and human hepatocytes. PLoS One. 2015 Mar 15.

Case studies

Inflammation:
Pernille Kristine Fisker Christensen, Axel Kornerup Hansen, Søren Skov, Britta Cathrina Martel, Jesper Larsen, Maria Helena Høyer-Hansen, Janne Koch.
Imiquimod induces skin inflammation in humanized BRGSF mice with limited human immune cell activity.
PLoS One. 2023 Feb 17

Safety:
Yan Li, Helene Strick-Marchand, Ai Ing Lim, Jiazi Ren, Guillemette Masse-Ranson, Dan Li, Gregory Jouvion, Lars Rogge, Sophie Lucas, Bin Li, James P Di Santo. Regulatory T cells control toxicity in a humanized model of IL-2 therapy. Nat Commun. 2017 Nov 24.

Immuno-oncology:
John J Tentler, Julie Lang, Anna Capasso, Deog Joong Kim, Ely Benaim, Young B Lee, Andrew Eisen, Stacey M Bagby, Sarah J Hartman, Betelehem W Yacob, Brian Gittleman, Todd M Pitts, Roberta Pelanda, S Gail Eckhardt, Jennifer R Diamond. RX-5902, a novel β-catenin modulator, potentiates the efficacy of immune checkpoint inhibitors in preclinical models of triple-negative breast Cancer. BMC Cancer. 2020 Nov 4.

Julie Lang, Anna Capasso, Kimberly R Jordan, Jena D French, Adwitiya Kar, Stacey M Bagby, Jacob Barbee, Betelehem W Yacob, Lia S Head, Kenneth D Tompkins, Brian M Freed, Hilary Somerset, Toshimasa J Clark, Todd M Pitts, Wells A Messersmith, S Gail Eckhardt, Margaret E Wierman, Stephen Leong, Katja Kiseljak-Vassiliades. Development of an Adrenocortical Cancer Humanized Mouse Model to Characterize Anti-PD1 Effects on Tumor Microenvironment. J Clin Endocrinol Metab. 2020 Jan 1.

A Capasso, J Lang, T M Pitts, K R Jordan, C H Lieu, S L Davis, J R Diamond, S Kopetz, J Barbee, J Peterson, B M Freed, B W Yacob, S M Bagby, W A Messersmith, J E Slansky, R Pelanda, S G Eckhardt. Characterization of immune responses to anti-PD-1 mono and combination immunotherapy in hematopoietic humanized mice implanted with tumor xenografts. J Immunother Cancer. 2019 Feb 8.

Drug screening:
Fournier N, Jacque E, Fontayne A, Derache D, Dupont G, Verhaeghe L, Baptista L, Dehenne A, Dezetter AS, Terrier A, Longue A, Pochet-Beghin V, Beghin C, Chtourou S, de Romeuf C. Improved in vitro and in vivo activity against CD303-expressing targets of the chimeric 122A2 antibody selected for specific glycosylation pattern. MAbs. 2018 May/Jun.

Infectiology:
Masse-Ranson G, Mouquet H, Di Santo JP. A Versatile Safeguard for Chimeric Antigen Receptor T-Cell Immunotherapies. Curr Opin HIV AIDS. 2018 Mar

Patent

Di Santo JP and Mention JJ. Dentritic cell-boosted humanized immune system mice. PCT/US/2010/029800. WO 2010/115115 A1. Patent 2010.

BRGSF-HIS variants

BRGSF-A2 HIS (genetically humanized for HLA-A2^HHD–Tg (HLA-A/H2-D/B2M)1Bpe)