Strain Background: C57BL/6N
The double-humanized PD-1 and VISTA mouse model (hPD-1/hVISTA) was generated by intercrossing hPD-1 and hVISTA mice. Both hPD-1 and hVISTA expressions are regulated by endogenous mouse promoters.
Research and Application:
The hPD-1/hVISTA 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/hVISTA 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.
Figure 1. hPD-1 expression pattern in hPD-1/hVISTA mice recapitulates mPD-1 in wild-type mice. hPD-1 and mPD-1 expression on αCD3/αCD28-activated splenocytes for (A) Tregs and (B) conventional CD4+, alongside both (C) hPD-1 expression and mPD-1 expression in CD8+ T cells across hPD-1/hVISTA mice and wild-type mice at the indicated timepoints.
Figure 2. hVISTA expression pattern in hPD-1/hVISTA mice recapitulates mVISTA in wild-type mice. hVISTA and mVISTA expression on freshly isolated splenocytes on Tregs, conventional CD4+, and CD8+ T cells.
Figure 3. Anti-tumor effects in response to anti-human VISTA + anti-mouse PD-1 treatment. Mice of indicated genotype were inoculated with MC38 tumor cells s.c. and treated αKLH (control), αmPD-1, αhVISTA or αmPD-1 + αhVISTA (combination). In wild-type mice, mPD-1 antibody can inhibit tumor proliferation, while hVISTA antibody can inhibit tumor proliferation in hVISTA mice. The combined antibody therapy of hVISTA and mPD-1 can inhibit tumor growth in hVISTA mice more effectively than either therapy used alone.
Figure 4. In vivo anti-tumor activity in response to pembrolizumab treatment in hPD-1 mice. Implanting GL261 murine glioma cells into wildtype and hPD-1 mice intracranially to detect the effects of different treatments on the survival of mice. In wild-type mice, hPD-1 and mPD-1 antibodies have no significant effect on the survival of mice, while in hPD-1 mice, the treatment of hPD-1 monoclonal antibody pembrolizumab can inhibit tumor growth and prolong the life of mice.