Preclinical Double-Humanized GITR/GITRL Mouse Model

Humanized Immune Checkpoint Mouse Models

Design of the hGITR/hGITRL mouse

The double-humanized GITR and GITRL mouse model (hGITR/hGITRL) was generated by intercrossing hGITR and hGITRL mice.

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.

Both hGITR and hGITRL expressions are regulated by endogenous mouse promoters.

Applications in immuno-oncology & immuno-inflammation

The hGITR/hGITRL mouse model enables in vivo efficacy assessment and profiling of agonist and antagonist antibodies targeting human immune checkpoint GITR and/or GITRL in fully immunocompetent mice.

 

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hGITR/hGITRL features

  • GITR and GITRL extracellular domains are entirely humanized
  • hGITR and hGITRL expression driven by the respective endogenous mouse promoter
  • Preservation of the target-ligand interaction
  • Fully functional mouse immune system
  • Lack of expression of the murine target gene, thus avoiding cross-reactivity

hGITR/hGITRL validation*

This model has been co-validated by our partners of the precompetitive consortium of company leaders in immuno-oncology and immunotherapy.

hGITR/hGITRL ICP model validation 1

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

Are you looking for another target?
Follow this link for humanized immune checkpoint (ICP) mouse models, or contact us.