Figure 1.
Effect of a combined therapy with antiangiogenic αv integrin antagonist and antitumor compartment-specific immunotherapy with antibody–IL-2 fusion proteins on primary tumors. Primary tumors were induced by s.c. injection (2 × 106) of each NXS2 neuroblastoma (A), CT26-KSA colon carcinoma (B), and B78-D14 melanoma cells (C). (Top) Treatment of established tumors (110–130 mm3) by daily i.v. injections of tumor-specific antibody–IL-2 fusion proteins huKS1/4-IL-2 (10 μg, colon carcinoma) and ch14.18-IL-2 (5 μg, neuroblastoma; 10 μg, melanoma) (5×) and continuous s.c. infusion of the vasculature-specific integrin αv antagonist or the control peptide with an osmotic pump for 7 days at 17.5 μg/h. The time of treatment initiation is indicated by a solid arrow. The size of the primary tumors of mice in each experimental group (n = 6) was determined by microcaliper measurements (width × length × width/2) (mean ± SE). The regression in primary tumor size of mice receiving the combination treatment compared with the size of established tumors at the time of treatment initiation was statistically significant in the three different syngeneic tumor models (P < 0.001, Wilcoxon Rank–Sum Test) in contrast to all controls (P > 0.05).