hPD-1/hCTLA-4 Mouse

Strain Background: C57BL/6N

Construction Strategy:

The double-humanized PD-1 and CTLA-4 mouse model (hPD-1/hCTLA-4) was generated by intercrossing hPD-1 and hCTLA-4 mice.

hPD-1/hCTLA-4:

• ■   The PD-1 and CTLA-4 extracellular domains are entirely humanized
• ■   Physiological regulation and expression pattern of the human PD-1 and CTLA-4
• ■   Preservation of the target-ligand interaction
• ■   Fully functional mouse immune system
• ■   Lack of expression of the murine target gene, thus avoiding cross-reactivity

Research and Application:

The hPD-1/hCTLA-4 mouse enables the in vivo efficacy and safety assessment of compounds targeting the human immune checkpoint PD-1 and/or VISTA in fully immunocompetent mice.

Use our hPD-1/hCTLA-4 mouse model together with 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.

Validation Data：

Figure 1. hPD-1 and hCTLA-4 expression patterns in hPD-1/hCTLA-4 mice recapitulate mPD-1 and mCTLA-4 in wild-type mice. Splenocytes from wildtype and hPD-1/hCTLA-4 double homozygous mice were activated with αCD3/αCD29. Expression of both hPD-1 and hCTLA-4 in CD4_conv T cells of hPD-1/hCTLA-4 mice, and mPD-1 and mCTLA-4 expression in CD4_conv T cells of wildtype mice are shown.    

Figure 2. hPD-1 and hCTLA-4 are expressed on TILs (tumor-infiltrating lymphocytes). PD-1 and CTLA-4 expression on TILs from mice bearing MCA205 tumors. Mouse and human PD-1 and CTLA-4 expression were analyzed on wild-type and hPD-1/hCTLA-4 mice.

Figure 3. Intracranial transplantation of GL261 murine glioma cells into wild-type and hPD-1/hCTLA-4 homozygous mice. After transplantation, wild-type mice are treated with mouse PD-1 monoclonal antibody and injection of αhPD-1 (pembrolizumab) in hPD-1/hCTLA-4 homozygous mice to inhibit tumor growth and extend the lifespan of the mice.

Figure 4. Subcutaneous transplantation of MC38 murine colorectal cancer cells into wild-type and hCTLA-4 homozygous mice. In hCTLA-4 mice, treatment with αhCTLA-4 (ipilimumab) injection can inhibit tumor growth and prolong the life of mice.