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.

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.