Preclinical humanized GITR mouse model
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Design of the hGITR mouse
The humanized GITR mouse model (hGITR) is developed by Knockin at the mouse GITR locus and driven by the endogenous promoter. It expresses a chimeric GITR with a human extracellular and murin intracellular domain. The human isoforms display diversity within the intracellular domain, and are expressed in case they support different signaling functions.
hGITR features
- The GITR extracellular domain is entirely humanized
- Physiological regulation and expression pattern of the human GITR
- Fully functional mouse immune system
- Lack of expression of the murine target gene, thus avoiding cross-reactivity
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Validation
hGITR expression is induced after stimulation
Expression of human GITR on aCD3/aCD28-stimulated splenocytes (2 days), analyzed by flow cytometry on Tregs, conventional CD4 (CD4conv), CD8 and B cells.
In vivo anti-tumor effect in response to anti-hGITR mAb treatment
hGITR homozygous mice with MB49 bladder cancer at day 0 were treated with vehicle or ahGITR mAb on days 7, 10 and 13. Tumor growth was followed until day 30. Unpaired t-test statistics: * p<0.05, ** p<0.005.
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hGITR
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hGITR/Foxp3
The hGITR/Foxp3 mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint GITR. The red fluorescent protein regulated under the Foxp3 promoter allows you to efficiently monitor and sort Foxp3-expressing cells from different lymphocyte lineages and lymphoid organs.
Preclinical humanized GITR mouse model
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