Figure 6
Intratumoral administration of OAV-scIL-12-TM reduces systemic exposure to scIL-12 and is less toxic than OAVs carrying other scIL-12 variants. Syrian hamsters bearing intrahepatic HaP-T1 tumors were treated with a single local administration of the indicated OAVs at different doses. (a) Blood was collected 24 h later to determine scIL-12 concentration. The dose of each virus is plotted in the horizontal axis of the graph. (b) Survival of animals 3 weeks after initiation of treatment. At this point, only treatment-related deaths were observed. White squares represent hamsters treated with 2 × 109 i.u. Ad-WT-Luc. (c) Representative microphotograph of paraffin-embedded lung samples from a hamster treated with 1 × 109 i.u. OAV-scIL-12. Hematoxylin–eosin staining (x200). Note the intense inflammatory infiltration and the accumulation of fluid in alveoli of the treated animal (asterisks), characteristic of lung edema. (d) Serum concentration of scIL-12 over time in hamsters treated with OAV-scIL-12-TM at the following doses: 2.5 × 108 i.u. (dotted gray line), 1 × 109 i.u. (solid gray line), 2 × 109 i.u. (dotted black line) and 5 × 109 (solid black line).
