Preclinical Triple-Humanized PD-1/GITR/GITRL Mouse Model
Design of the hPD-1/hGITR/hGITRL mouse
The triple-humanized PD‑1, GITR and GITRL mouse model (hPD-1/hGITR/hGITRL) was generated by intercrossing hPD-1, hGITR and hGITRL mice.
hPD-1 was generated by inserting, within the mouse Pd-1 locus, a chimeric PD-1 with the human extracellular and murine transmembrane and intracellular domains.
hGITR was developed by inserting, within the mouse Gitr locus, a chimeric GITR with the human extracellular and the murine intracellular domain.
hGITRL was generated by inserting, within the mouse Gitrl locus, a chimeric GITRL with the human extracellular and the murine intracellular domain.
hPD-1, hGITR and hGITRL expressions are regulated by endogenous mouse promoters.
Applications in immuno-oncology & immuno-inflammation
The hPD-1/hGITR/hGITRL mouse model enables in vivo efficacy assessment and profiling of antibodies targeting human immune checkpoint PD-1, GITR and/or GITRL in fully immunocompetent mice.
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- PD-1, GITR and GITRL extracellular domains are entirely humanized
- hPD-1, hGITR and hGITRL expression driven by the respective endogenous mouse promoter
- Fully functional mouse immune system
- Lack of expression of the murine target genes, thus avoiding cross-reactivity
This model has been co-validated by our partners of the precompetitive consortium of company leaders in immuno-oncology and immunotherapy.
hPD-1 is expressed on T cells
Freshly isolated splenocytes from wild-type or PD-1/GITR/GITRL triple-humanized mice. mPD-1 and hPD-1 expression were analyzed on single live CD3+, CD4+CD25- cells (conv CD4) and CD4+CD25+Foxp3+ cells (Treg). T cells from lymphocytes incubated in the presence of anti-CD3, anti-CD28 and recombinant murine IL-2.
hGITR is expressed on T cells
Freshly isolated splenocytes from wild-type or PD-1/GITR/GITRL triple humanized mice. mGITR and hGITR expression were analyzed on single live CD3+, CD4+CD25- cells (conv CD4) and CD4+CD25+Foxp3+ cells (Treg). Cells from lymphocytes were incubated in the presence of anti-CD3, anti-CD28 and recombinant murine IL-2.
In vivo anti-tumor activity is observed in response to anti-PD-1 treatment in hPD-1 mice
Survival of mice of indicated genotype implanted intracranially with GL261 murine glioma cells and treated with αhPD-1 (pembrolizumab), αmPD-1 or isotype (Mantel-Cox test: ***p<0.001).
hGITR-Fc significantly inhibits ear swelling at 24 and 48 hours post DNFB challenge in hGITR/hGITRL mice
Mice were injected with vehicle, IgG, GITR-Fc or mCTLA4-Ig on day -1, sensitized with DNFB on day 0, and then challenged on the ear on day 5. The mean ear-swelling response was determined at 24 and 48 hours post DNFB challenge.
* For more validation data please contact us.
Ready to be shipped to your lab
- Cohorts available upon request
- Studies can be carried out at your site or at your favorite CRO
- SOPF certification and worldwide delivery by professional breeders
- Models provided with FTO on patent-protected technologies used for model generation
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