Humanized Immune Checkpoint (ICP) Mouse Models

Humanized Immune Checkpoint Mouse Models

Therapies targeting immune checkpoints (ICPs) are changing the practice of medical oncology. genOway has developed a catalog of reliable and efficient translational mouse models for immunotherapy expressing humanized immune checkpoints.

Applications

These models are suitable to assess the efficacy of immuno-oncology compounds targeting immune checkpoints in fully immunocompetent mice. Moreover, they represent a powerful model system for studying how compounds modulate immune cell response and/or stroma cells in a physiological microenvironment.

  • Cohorts available upon request
  • Studies can be carried out at your site or at your favorite CRO
  • VAF Elite/SOPF certification and worldwide delivery by professional breeders
  • Models provided with FTO on patent-protected technologies used for model generation

Model features

  • Physiological expression of the human target(s)
  • Preservation of the target-ligand interaction
  • Fully functional mouse immune system
  • Lack of expression of the murine target gene, thus avoiding cross-reactivity
  • Suitable for studying:
    • Well-calibrated syngeneic tumor models
    • Long-term treatment(s)
    • T cell exhaustion and reminiscence

Model validation

The ICP mouse models are co-validated by our partners of the precompetitive consortium, including BMS, Charles River, Alligator and more company leaders in immuno-oncology and immunotherapy.

Presse

Read the press release:
genOway announces the consolidation of a precompetitive consortium to develop and validate humanized immune checkpoint mouse models.


Model catalog

Single-targeted immune checkpoint mouse models


hPD-1 mice

Target: PD‑1                    

The humanized PD-1 mouse model (hPD-1) expresses human PD-1 instead of murine PD-1 while the regulation of PD-1 expression is kept under the mouse promoter. The anti-tumor effect induced by anti-hPD-1 antibody pembrolizumab is shown using our model. 

hCTLA-4

Target: CTLA-4                    

The human CTLA-4 expression recapitulates the mouse CTLA-4 expression on T cells. An anti-tumor response, induced by anti-hCTLA-4 ipilimumab, is observed in hCTLA-4-expressing mice.

hVISTA

Target: VISTA                  

The human VISTA expression pattern in homozygous mice is similar to murine VISTA in wild-type mice. Moreover, the model has been shown to be functional in vivo, because the combination of anti-hVISTA and anti-mPD-1 therapies increases survival in a MC38 tumor model. 

hOX40

Target: OX40                   

The human OX40 expression mirrors the murine OX40 expression. hOX40 is functional and hOX40L induces increased T-cell proliferation in vitro. Furthermore, anti-tumor effect induced by an anti-hOX40 antibody (BMS 986178 analog) was observed in a MC38 tumor model.

hGITR

Target: GITR                    

hGITR is detected on activated splenocytes and tumor-infiltrating lymphocytes (TILs). The model is functional as it has been used to show the anti-tumor effect of an anti-hGITR antibody.

hLIGHT

Target: LIGHT                    

The human LIGHT expression mirrors the murine LIGHT expression. hLIGHT is functional and its stimulation increases T-cell activation in vivo

hCD28

Target: CD28                    

The human CD28 expression recapitulates murine CD28 expression. hCD28 is functional: α-human CD28 co-stimulation induces T cell activation and proliferation. 

hCD39

Target: CD39                    

The human CD39 expression recapitulates murine CD39 expression. hCD39 is functional: α-human CD39 specifically reduces human CD39 activity.

hSTING

Target: STING                    

The humanized STING model, developed by Knockin at the mouse STING locus, expresses a full human STING. hSTING is functional: Agonists induce cytokine release in vivo. 

Double-targeted immune checkpoint mouse models


hCD3eps-hCD28

Target: CD3ε & CD28                    

The double-humanized CD3ε/CD28 mouse model (hCD3ε/hCD28) expresses the human epitope of the CD3ε chain and a chimeric CD28 with a human extracellular domain. This model was generated by intercrossing hCD3ε and hCD28 mice.

hPD-1-hTIM3

Target: PD‑1 & TIM3                    

The double-humanized PD-1/TIML3 mouse model (hPD-1/hTIM3) expresses human PD-1 and human TIM3 instead of murine proteins while its regulation is kept under the mouse promoter. This model was generated by intercrossing hPD-1 and hTIM3 mice.

hPD-1-VISTA

Target: PD‑1 & VISTA                    

The double-humanized PD-1/VISTA mouse model (hPD-1/hVISTA) expresses human PD-1 and VISTA instead of murine proteins while its regulation is kept under the mouse promoter. This model was generated by intercrossing hPD-1 and hVISTA mice.

hPD-1-hCTLA-4

Target: PD‑1 & CTLA-4                    

The double-humanized PD-1/CTLA-4 mouse model (hPD-1/hCTLA-4) expresses human PD-1 and CTLA-4 instead of murine proteins while its regulation is kept under the mouse promoter. This model was generated by intercrossing hPD-1 and hCTLA-4 mice.

hCTLA-4-LAG3

Target: CTLA-4 & LAG3                    

The double-humanized CTLA-4/LAG3 mouse model (hCTLA-4/hLAG3) expresses human CTLA-4 and LAG3 instead of murine proteins while its regulation is kept under the mouse promoter. This model was generated by intercrossing hCTLA-4 and hLAG3 mice.

hGITR-Foxp3

Target: GITR & Foxp3                    

hGITR mice were crossed with Foxp3-IRES-mRFP (FIR) reporter mice to monitor Treg activity. The FIR's bicistronic reporter expressing a red fluorescent protein has been knocked into the endogenous Foxp3 locus and faithfully mirrors Foxp3 expression.

hGITR-hGITRL

Target: GITR & GITRL                    

The double-humanized GITR/GITRL mouse model (hGITR/hGITRL) expresses both human GITR and GITRL instead of their corresponding murine proteins. Both genes are under endogenous mouse promoters. This model was generated by intercrossing hGITR and hGITRL mice.

 

Further reading

 

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