Preclinical Double-Humanized PD-1/PD-L1 Mouse Model

Humanized Immune Checkpoint Mouse Models

Design of the hPD-1/hPD-L1 mouse

The double-humanized PD‑1 and PD-L1 (hPD-1/hPD-L1) mouse model was generated by intercrossing hPD-1 and hPD-L1 mice.

The PD-1 humanized model, developed by Knockin at the mouse Pd-1 locus, expresses a chimeric PD-1: human extracellular and mouse transmembrane and intracellular domains.

The hPD-L1 humanized model, developed by Knockin at the mouse Pd-L1 locus, expresses a chimeric PD-L1 (human extracellular domains and murine transmembrane and intracellular domains).

Both hPD-1 and hPD-L1 expressions are regulated by endogenous mouse promoters.

Applications in immuno-oncology & immuno-inflammation

The hPD-1/hPD-L1 mouse model enables in vivo efficacy assessment and profiling of molecules targeting the human PD-1/PD-L1 axis in fully immunocompetent mice.


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hPD-1/hPD-L1 features

  • PD-1 and PD-L1 extracellular domains are entirely humanized
  • hPD-1 and hPD-L1 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

hPD-1/hPD-L1 validation*

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

hPD-1/hPD-L1 ICP model validation 1

hPD-1 expression regulation is preserved in the double-humanized model hPD-1/hPD-L1

Splenocytes from hPD-1/hPD-L1 double homozygous mice and wild-type mice were activated with αCD3/αCD28 and cultured in presence of recombinant mIL-2. mPD-1 and hPD-1 expression was evaluated at day 0 and 2 on conventional CD4 T cells (viable, CD3+CD4+Foxp3-) and CD8 T cells (viable, CD3+CD8+Foxp3-).

hPD-1/hPD-L1 ICP model validation 2

hPD-L1 is expressed on immune cells

Splenocytes from hPD-1/hPD-L1 and wild-type mice were treated or not (NT) for 24 hours with recombinant mouse IFN-γ. Fluorescence intensity (MFI) of mPD-L1 and hPD-L1 was evaluated on monocytes (CD3-CD19-CD11c-CD11b+) and T cells (viable, CD3+CD19-).

In vivo anti-tumor activity in response to Atezolizumab in hPD-1/hPD-L1 mice

hPD-1/hPD-L1 ICP model validation 3hPD-1/hPD-L1 ICP model validation 3b

* 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

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