Preclinical Double-Humanized PD-1/LAG3 Mouse Model

Humanized Immune Checkpoint Mouse Models

Design of the hPD-1/hLAG3 mouse

The double-humanized PD‑1 and LAG3 (hPD-1/hLAG3) mouse model was generated by intercrossing hPD-1 and hLAG3 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 LAG3 humanized model, developed by Knockin at the mouse Lag3 locus, expresses the full-length chimeric LAG3 isoform (human extracellular domains, and mouse transmembrane and intracellular domains).

Both hPD-1 and hLAG3 expressions are regulated by endogenous mouse promoters.

Applications in immuno-oncology & immuno-inflammation

The hPD-1/hLAG3 mouse model enables in vivo efficacy assessment and profiling of antibodies targeting human immune checkpoint PD-1 and/or LAG3 in fully immunocompetent mice.

 

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hPD-1/hLAG3 features

  • PD-1 and LAG3 extracellular domains are entirely humanized
  • hPD-1 and hLAG3 expression driven by the respective endogenous mouse promoter
  • Fully functional mouse immune system
  • Lack of expression of the murine target gene, thus avoiding cross-reactivity

hPD-1/hLAG validation*

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

hPD-1/hLAG3 ICP model validation 1

hPD-1 is expressed on hPD-1/hLAG3 lymphocytes

Splenocytes from hPD-1/hLAG3 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 3 on conventional CD4 T cells (viable, CD3+CD4+Foxp3-), Treg cells (viable, CD3+CD4+CD25+Foxp3+) and CD8 T cells (viable, CD3+CD8+).

hPD-1/hLAG3 ICP model validation 2

LAG3 is expressed on hPD-1/hLAG3 lymphocytes

Splenocytes from hPD-1/LAG3 double homozygous mice and wild-type mice were activated with αCD3/αCD28 and cultured in presence of recombinant mIL-2. mLAG3 and hLAG3 expression was evaluated at day 3 on conventional CD4 T cells (viable, CD3+CD4+Foxp3-), Treg cells (viable, CD3+CD4+CD25+Foxp3+) and CD8 T cells (viable, CD3+CD8+).

In vivo anti-tumor activity in response to combination of anti-human PD-1 and anti-human LAG3 in hPD-1/hLAG3 mice

hPD-1/hLAG3 ICP model validation 3hPD-1/hLAG3 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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