Fig. 7
Triple combination of MEK inhibition and agonist immunotherapy plus anti PD-1 checkpoint blockade leads to enhanced efficacy in AT3ova and 4T1Ch9 tumor bearing mice. Mice (n = 6 per group) bearing established 4T1Ch9 (a–d) or AT3ova (e, f) tumors were treated with a double combination of trametinib via daily oral gavage for 20 days (AT3ova) or 15 days (4T1Ch9) and either α-4-1BB, α-OX-40, or α-PD-1 antibody or triple combination of trametinib and either agonist (α-4-1BB, α-OX-40) in combination with α-PD-1 antibody; three doses (4T1Ch9) or four doses (AT3ova) via IP injection on days 0, 4, 8, and 12 or combination of trametinib and agonists. a, b Tumor growth volume (mm3) in the 4T1Ch9 model and survival (n = 6) in the 4T1Ch9 (c, d) and AT3ova (e, f) were monitored. End point was determined as when tumors reached an ethical limit of 1400 mm3 (mean tumor volume ± SEM). Controls groups are duplicated between panels as these experiments were performed concurrently. P-values represent two-way ANOVA, post hoc Tuckey’s tests for tumor growth, and log ranked (Mantel–Cox) test for survival proportions. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001
