Figure 4 from Inhibition of Notch4 Using Novel Neutralizing Antibodies Reduces Tumor Growth in Murine Cancer Models by Targeting the Tumor Endothelium

Treatment of tumors with 6-3-A6/E7011 delays tumor growth in syngeneic tumor models which express endothelial Notch4. A, IF staining of murine Lewis lung carcinoma, murine Py8119 breast carcinoma, and murine B16F10 melanoma with Notch4 and CD31. Arrowheads indicate Notch4-expressing vessels (scale bar = 200 μm). B and C, Preventative strategy using Py8119 tumor cells orthotopically implanted into the mammary fat pad and treated with B, E7011 (n = 18 human IgG, n = 17 E7011) or C, 6-3-A6 (n = 4) twice weekly starting 12 hours following tumor implantation. D and F, Tumor growth curve of subcutaneously implanted D, Lewis lung (n = 4) and E, B16F10 (n = 7) treated intravenously with E7011 (25 mg/kg twice weekly) and orthotopically implanted F, Py8119 murine breast carcinomas (n = 5) treated intravenously with 6-3-A6 (25 mg/kg twice weekly) once the average tumor volume of each cohort had reached approximately 30 mm³. Statistical analysis performed with two-way ANOVA for tumor growth curves, plotted as average ± SEM; *, P < 0.05; ***, P < 0.001. TNBC, triple-negative breast cancer.