Figure 1.

Macrophages Prevent Successful i.v. Delivery of VVL15 to Tumors

(A) Quantification of whole-body IVIS imaging, in which luminescence was observed and quantified from tumors of VVL15-infected immunocompetent BALB/c mice bearing CT26 flank tumors (n = 3/group) following single i.v. administration of 1 × 10⁸ PFU of VVL15, containing a luciferase reporter protein, or PBS. (B) Immunohistochemical staining for VV coat protein in the spleen, 3 and 8 h after i.v. administration of 1 × 10⁸ PFU of VVL15 (dark brown areas). Stained spleens from PBS-infected animals are shown for reference. Original magnification, ×200 (n = 3/group). (C) Representative confocal image of a VV-infected spleen of an immunocompetent mouse showing the co-localization of VV and macrophages. Macrophages and VV were detected by staining for CD68 and VV coat protein, respectively, 48 h after i.v. delivery of VVL15. Three mice per group were analyzed. Scale bars, 10 μm. (D) Quantification of tumor-specific VVL15 using whole-body IVIS imaging of BALB/c mice with subcutaneous tumors after intra-peritoneal (i.p.) injection of PBS, PBS/liposomes, or clodronate liposomes at 24, 72, and 144 h prior to i.v. injection of 1 × 10⁸ PFU of VVL15 (n = 5/group). Significance of groups in comparison to clodronate liposomes + VVL15 is shown. Data are presented as mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 (one-way ANOVA with Newman-Keuls multiple comparison test).