Figure 4.
Combinatorial and triple blockade of PD-1, CTLA-4, and LAG-3 pathways exerts differential antitumor immunity. (A) Experimental scheme and antibody blockade treatment. C57BL/6 mice were implanted with IE9mp1 tumors as described in Fig. 3, randomized and treated with control IgG, single antibody, and combination of two or three antibodies were administered every other day for six times (Materials and Methods). Tumor progression was monitored by measuring the abdominal circumference due to accumulation of ascites. Survival was determined when the abdominal circumference reached 12 cm or moribund. (B) Combinatorial blockade of PD-1/LAG-3 or CTLA-4/LAG-3 pathways mildly improve antitumor immunity. Antibody treatment was as described above. Survival data were analyzed with the Mantel–Cox log-rank test. Data were obtained from 14 to 15 mice per group and were representative of two independent experiments. (C) Triple blockade of three checkpoints and dual antibody blockade of PD-1 and CTLA-4 significantly enhanced the survival of ovarian tumor-bearing wild-type mice. Antibody treatment and data analysis were performed at the same time as that described in (B).