
Figure 1: Human PD-1 or human CTLA-4 expression on T cells is confirmed by FACS analysis in single KI HuGEMM models.
Evaluate combinations of checkpoint inhibitors in vivo with humanized drug target mouse models
HuGEMM humanized PD-1/CTLA-4 mice provide a translational model for testing human-specific combination therapies. This double knock-in model has both humanized PD-1 and CTLA-4 receptors within a functional mouse immune system.
The PD-1/CTLA-4 double knock-in model was developed by breeding two single knock-in models, the PD-1 and CTLA-4 mice, which express either human PD-1 and CTLA-4 under the respective endogenous murine promoters. This supports the in vivo evaluation of human-specific combination therapies, blocking multiple immune checkpoints simultaneously.
Figure 1: Human PD-1 or human CTLA-4 expression on T cells is confirmed by FACS analysis in single KI HuGEMM models.
Figure 1: Human PD-1 or human CTLA-4 expression on T cells is confirmed by FACS analysis in single KI HuGEMM models.
Figure 2: Validation of efficacy of human-specific anti-PD-1 and anti-CTLA-4 antibodies: Combination anti-PD-1 + anti-CTLA-4 results in complete remission. Cured mice remain disease free up to 40 days post grouping. Rechallenge of cured mice with tumor cells implanted in the left flank results in memory response with tumors failing to grow.
Figure 2: Validation of efficacy of human-specific anti-PD-1 and anti-CTLA-4 antibodies: Combination anti-PD-1 + anti-CTLA-4 results in complete remission. Cured mice remain disease free up to 40 days post grouping. Rechallenge of cured mice with tumor cells implanted in the left flank results in memory response with tumors failing to grow.