Inhibition of paracrine VEGFR-2 pathway reduces growth of established lymphoma xenografts in NOD/SCID mice and correlates with decreased tumor angiogenesis. (A) NOD/SCID mice engrafted with subcutaneous RL and SKI-DLBCL1 lymphoma tumors were treated with IVIG, anti–human VEGFR-2 (IMC-1C11), anti–murine VEGFR-2 (DC101), or DC101 + IMC-1C11 antibodies (n = 5-10 mice/group). Results were statistically significant (P < .05) for IVIG compared with DC101 on days 15 to 21 in both models. (B, C) Lymphoma xenografts from mice treated with IVIG, IMC-1C11, DC101, or DC101 + IMC-1C11 were stained with antibodies for CD34 (10 ×,20 ×), FVIII (von Willebrand factor 10 ×), and CD31 (10 ×). DC101 treatment decreased the number of vascular endothelial cells in vessels (von Willebrand factor and CD34 expression) and overall microvessel density (CD31⁺ and CD34⁺ vessels) compared with IVIG or IMC-1C11 treatment. Error bars indicate standard error of mean tumor volume.