Figure 4.

Inhibition of nonirradiated lung metastasis by local radiation of subcutaneously implanted tumors and treatment with VEGF-4–1BB aptamer conjugates. 4T1 tumor cells were implanted subcutaneously in the right flank of Balb/c mice, and 8 days later mice were injected intravenously with 4T1 cells. Five days after intravenous injections when the subcutaneously growing tumors reached an average size of 75 mm³, they were irradiated with 12 Gy and 3 days later treated with VEGF-4–1BB aptamer conjugates or with a mixture of VEGF and 4–1BB aptamers three times 2 days apart. Five days before irradiation, 4T1 tumor cells were injected intravenously to establish métastasés in the lung. Mice were sacrificed when mice in the control group showed signs of morbidity (21 days post-intravenous tumor administration) and tumor burden was determined. A, Volume of subcutaneously implanted tumor at day of sacrifice. B, Time course of subcutaneous tumor growth. C, Lung weights measured when mice were sacrificed.