Preclinical Double-Humanized PD-1/LAG3 Mouse Model
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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- 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
This model has been co-validated by our partners of the precompetitive consortium of company leaders in immuno-oncology and immunotherapy.
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+).
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
* 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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