Figure 2.

Combination of radiation with 4-1BB antibody, but not with VEGF-4–1BB aptamer conjugate, elicits nonspecific immune responses and inflammation. Balb/c mice were injected subcutaneously with 4T07 tumor cells and when they reached an average diameter of 75 mm3, tumors were irradiated. One hundred pmol (1×) of VEGF-4–1BB aptamer conjugate or 800 pmol (8×) of either 4–1BB antibody or IgG isotype control was administered 6 days later via the tail vein three times 2 days apart. Mice were sacrificed 5 days following the last administration. Liver (A) and spleen (B) weight. Percentage of CD8+ cells in the liver (C) and spleen (D). E and F, Serum IFNγ (E) and percentage of intracellular granzyme B-expressing CD8+ cells (F). Tissue sections from the lung (G) and liver (H) were stained with hematoxylin and eosin and visualized by light microscopy. Arrows, H&E staining inflammatory foci in the liver treated with 100 pmol (1×) of 4–1BB antibody. I, ALT and AST levels in the circulation 14 days after irradiation (3 mice/group). NS, nonsignificant.