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首页 模型资源 免疫系统重建模型 BRGSF-A2-HIS

Design of the BRGSF-A2-HIS mouse

The BRGSF-A2 model is generated by inserting a human leukocyte antigen serotype A2 (HLA-A2) class I transgene in the genome of BRGSF (Balb/c Rag2tm1Fwa IL2rγtm1Cgn SirpαNOD Flk2tm1Irl) mice. These mice are subsequently used as recipients to reconstitute a functional human immune system (HIS) to create BRGSF-A2-HIS mouse models.

Applications

The presence of HLA molecules on BRGSF-A2-HIS thymic epithelial cells hinders T cell cross-reactivity, making this model an invaluable tool to study:

  • Human cytotoxic T lymphocyte responses against human infectious diseases and malignancies
  • Preclinical efficacy of immunotherapies
  • Mechanisms regulating the expression of senescence biomarkers
 
 
 
 

BRGSF-A2-HIS features

The BRGSF-A2-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 dendritic cells (pDCs) and monocytes/macrophages.

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  • Highly permissive to human xenograft, including primary or established tumor cells (CDX or PDXs) by virtue of the SIRPαNOD 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
  • A robust model to study T-cell responsiveness to infection- or tumor-associated antigens in the context of the human MHC molecules

  • BRGSF-A2-HIS mice display a strongly humanized expression profile in blood and lymphoid tissues

    Representative dot plots showing the relative proportion of murine and human CD45 (mCD45 and hCD45, respectively) cells in peripheral blood mononuclear cells (PBMC), splenocytes (SP), and bone marrow (BM) cells of 16-19-week-old BRGSF-A2-HIS mice.

     

  • Similar distributions of naive, memory and effector T cells in blood samples of BRGSF-A2-HIS mice and human healthy donors

    In the graphs are reported the frequency of naive (white bars), memory (gray bars) and effector (black bars) T cells in the blood of BRGSF-A2-HIS mice (HIS) and healthy donors (HD).

     

  • BRGSF-A2-HIS mice recapitulate human senescence and exhaustion profiles

    Frequency of CD57+ (A), KLRG1+ (B), PD-1+ (C) and TIGIT+ (D) cells among naive (white bars), memory (gray bars), and effector (black bars) human CD4+ and human CD8+ T cell subsets in peripheral blood mononuclear cells (PBMC), splenocytes (SP), and bone marrow (BM) preparations of BRGSF-A2-HIS mice (HIS) and healthy donors (HD).

     

更多详细数据请联系我们：联系我们 - 基锘威 - genOway (my3w.com)

案例

  1. Homeostasis of monocytes and lung interstitial macrophages is regulated by collagen domain-binding receptor LAIR1 in vivo
  2. Predictive in vivo evaluation of immunotherapy efficacy: tHIS is a reliable model
  3. Deciphering high-dose IL-2 toxicity in reconstituted HIS mice

评论

  1. Myeloid and dendritic cells enhance therapeutics-induced cytokine release syndrome features in humanized BRGSF-HIS preclinical model
  2. Targeting myeloid cells in the tumor microenvironment in BRGSF-HIS mice
  3. Assessing T-cell engagers efficacy in vivo: Versatility of BRGSF-HIS mice
  4. Expression of druggable myeloid targets in the BRGSF-HIS preclinical model
  5. Functional human myeloid compartment in BRGSF-HIS preclinical model
  6. Assessing T-cell engagers in vivo: How BRGSF-HIS mice can help
  7. Challenging the predictability of preclinical models for assessment of T-cell engagers
  8. Targeting tumor-associated myeloid cells: The new grail in immuno-oncology?
  9. Immunotherapy efficacy assessment and metastases studies: tHIS model is highly permissive to engraftment
  10. Cytokine release syndrome (CRS)
  11. Define “humanized”: two mouse models helping produce cancer immunotherapies
  12. Part 1: Toward a better effective preclinical model in immuno-oncology
  13. Tumor grafts in preclinical research: Models, models, overall, who is the fittest of them all?
  14. Part 3: BRGSF-HIS, a new human immune system mouse model for immuno-oncology studies

已发文献

  1. VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response

海报

  1. Functional human myeloid cells in BRGSF-HIS humanized mice enable myeloid-directed therapy assessment
  2. CD3 humanized mouse models as validated tools to assess immune-related adverse events of T-cell engagers
  3. Anti-VISTA agents profiling: complementarity of BRGSF-HIS and hVISTA Knock-in as preclinical models for immunotherapies
  4. Translatable preclinical mouse models for assessment of T-cell engager-induced CRS
  5. Cell-depleting agents assessment in preclinical models