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Strain Background: C57BL/6N

 

Construction Strategy:

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

 

Strain Description:

  •   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

 

Research Application:

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

 

Validation Data:

hPD-1/hTIM3 Mouse Img1

Figure 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 pregated on lymphocytes, single cells, living cells, CD45+/TCRb+, and CD8+.  

 

hPD-1/hTIM3 Mouse Img2

Figure 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.

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