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. 2020 Mar 24;8(1):e000710. doi: 10.1136/jitc-2020-000710

Figure 2.

Figure 2

vvDD-IL-12-FG treatment produces tethered IL-12 in tumors and is safe and effective in therapeutic tumor models. B6 mice were intraperitoneally inoculated with 5×105 MC38-luc cells and treated with PBS, vvDD, vvDD-IL-12, vvDD-IL-12-FG, or vvDD-IL-12-RG at 1×109 PFU/mouse 9 days post-tumor inoculation. The mice treated above were sacrificed at day 5 after treatment. Tumor nodules were collected to measure the amount of IL-12 (A) and IFN-γ in tumor (B); the lungs and kidneys were collected to monitor pulmonary tissue edema (C and D); sera were collected to measure AST (E) and ALT (F) in sera. (G) B6 mice were intraperitoneally inoculated with 5×105 MC38-luc cells and treated with PBS, vvDD, vvDD-IL-12, or vvDD-IL-12-FG at 2×108 PFU/mouse 5 days post-tumor inoculation (n≥8). The vvDD-IL-12-FG cured mice were subcutaneously re-challenged with MC38 (H) or LLC (I). B6 mice were intraperitoneally inoculated with 5×105 MC38-luc cells and treated with PBS or indicated viruses at 2×108 PFU/mouse 9 days post-tumor inoculation (n≥23). The survival curve was shown (J). Some of these treated mice were sacrificed and splenocytes were restimulated with mitomycin C-inactivated MC38 cells to monitor IFN-γ production (K). (L) BALB/c mice were intraperitoneally inoculated with 4×105 AB12-luc cells and treated with PBS or indicated viruses at 2×108 PFU/mouse 9 days post-tumor inoculation (n≥10). A log-rank (Mantel–Cox) test was used to compare survival rates. *P<0.05; **P<0.01; ***P<0.001; and ****P<0.0001. ALT, alanine transaminase; AST, aspartate transaminase; IFN-γ, interferon γ; IL-12, interleukin 12; NS, not significant; PBS, phosphate-buffered saline; PFU, plaque-forming units.