Figure 5.
NSC.CF33 Improves CF33 Distribution In Vivo
(A) Seven days after i.p. treatment, NSCs remarkably increase infection and replication of CF33.FFLUC in the ovcar8 NSG orthotopic mouse model. (B) NSCs maintain CF33.FFLUC BLI after the second round of treatment compared with the free CF33.FFLUC-treated group that lost 2/3 of their signal. BLI signal was acquired 1 h after the first and second treatment rounds. Error bars represent the SEM. (C) Tumors with adjacent tissue were harvested 2 days after the first treatment, and a representative micrograph of a tumor mass (black dotted line) stained with FFLUC antibody-DAB (brown) on the surface of normal omentum. A sister serial section of the section shown was stained with an anti-pox antibody-DAB (brown). This staining pattern suggests that CF33 delivered by NSCs spreads through tumors from the periphery inward (black arrows). Scale bars: 200 μm. (D) C57BL/6 mice with established i.p. ID8 tumors with NSC.CF33 (2 × 106), free CF33 with matched viral load 3 × 106 plaque-forming units (PFUs), or PBS control. Immunofluorescence staining with anti-vaccinia Ab (red) confirmed transfer of CF33 (red) to tumor (green) in the NSC.CF33 group and free CF33 group with matched viral loads (3 × 106 PFUs/mouse), compared with the untreated group, 4 days after the first treatment. Scale bar: 100 μm.