Preclinical Double-Humanized PD-1/TIM3 Mouse Model

Humanized Immune Checkpoint Mouse Models

Design of the hPD‑1/hTIM3 mouse

The double-humanized PD-1 and TIM3 mouse model (hPD-1/hTIM3) was generated by intercrossing hPD-1 and hTIM3 mice.

hPD-1 has been developed by inserting, within the mouse PD-1 locus, a chimeric PD-1 with a human extracellular domain, a murine transmembrane domain and a murine intracellular domain.

The design of the TIM3 humanized model, developed by Knockin at the mouse TIM3 locus, enables the expression of a chimeric TIM3 with a human extracellular domain, a murine transmembrane domain and a murine intracellular domain.

Applications in immuno-oncology

The hPD-1/hTIM3 mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint PD-1 and/or TIM3 in fully immunocompetent mice.

Humanized tumor cell line MC38-hPD-L1:
Use our hPD-1/hTIM3 mouse model together with our cell line MC38-hPD-L1 as a syngeneic tumor model for testing the efficacy of combination therapies targeting human PD-1 and human PD-L1.

 

Request a quote here to get pricing, offers and hPD-1/hTIM3 model information by phone or email.

 

hPD-1/hTIM3 features

  • The PD-1 and TIM3 extracellular domains are entirely humanized
  • 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/hTIM3 validation*

hPD-1+hTIM3 ICP model validation 1

hPD-1 and hTIM3 expression on tumor-infiltrated CD8 T cells

Human TIM3 and human PD-1 expression on CD8 T cells isolated from tumor. Tumors were harvested 28 days post inoculation of MC38 cells in hPD-1/hTIM3 mice. Isolated cells were pre-gated on lymphocytes, single cells, living cells, CD45+/TCRβ+, and CD8+.

hPD-1+hTIM3 ICP model validation 2

Anti-human TIM3 therapy in combination with anti-human PD-1 improves tumor protection when compared to vehicle or blocking PD-1 only.

Survival of hPD-1/hTIM3 mice implanted subcutaneally with MC38 cells and treated with vehicle, αhPD-1, or αhPD-1 + αhTIM3 (two-way ANOVA; ****p<0.0001; ns: non-significant).

* For more validation data, please consult our hPD-1 webpage, or  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
  • VAF Elite/SOPF certification and worldwide delivery by professional breeders
  • Models provided with FTO on patent-protected technologies used for model generation


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