Humanized Immune Checkpoint (ICP) 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
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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
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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. |
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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. |
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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. |
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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. |
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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. |
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Target: LIGHT The human LIGHT expression mirrors the murine LIGHT expression. hLIGHT is functional and its stimulation increases T-cell activation in vivo. |
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Target: CD28 The human CD28 expression recapitulates murine CD28 expression. hCD28 is functional: α-human CD28 co-stimulation induces T cell activation and proliferation. |
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Target: CD39 The human CD39 expression recapitulates murine CD39 expression. hCD39 is functional: α-human CD39 specifically reduces human CD39 activity. |
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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
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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. |
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Target: PD‑1 & PD-L1 The double-humanized PD-1/PD-L1 mouse model (hPD-1/hPD-L1) expresses human PD-1 and human PD-L1 instead of murine proteins while its regulation is kept under the mouse promoter. This model was generated by intercrossing hPD-1 and hPD-L1 mice. |
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Target: PD‑1 & LAG3 The double-humanized PD-1/LAG3 mouse model (hPD-1/hLAG3) expresses human PD-1 and human LAG3 instead of murine proteins while its regulation is kept under the mouse promoter. This model was generated by intercrossing hPD-1 and hLAG3 mice. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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. |
Triple-targeted immune checkpoint mouse models
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Target: PD-1 & GITR & GITRL The triple-humanized PD-1/GITR/GITRL mouse model (hPD-1/hGITR/hGITRL) expresses human PD-1, GITR and GITRL instead of their corresponding murine proteins. The genes are under endogenous mouse promoters. This model was generated by intercrossing hPD-1, hGITR and hGITRL mice. |
Further reading
- Tumor grafts in preclinical research: Models, models, overall, who is the fittest of them all?
- Uncoupling Efficacy from Toxicity: A Case Study on MEDI5752
- Uncoupling Toxicity from Therapeutic Efficacy: A Case Study on ATOR-1015
- Uncoupling Toxicity from Therapeutic Efficacy: The New Challenge of Immunotherapies
- Define "Humanized": Two Mouse Models Helping Produce Cancer Immunotherapies
- Humanized Immune Checkpoint Mouse Models for Immuno-Oncology Studies
- A new Nature report by Bristol-Myers Squibb provides new insights into VISTA biology and design of combination therapies
- Immune checkpoint inhibitors: A strategy to tackle cancer?
Are you looking for another target? Get in touch with us.