Figure 4. Optimized combination therapy results in synergistic anticancer activity.
(a) Renca (left) or MC38 (right) tumors were implanted into Balb/c or C57/Bl6 mice respectively. Mice were injected with PBS or 2×108 pfu of B18R- oncolytic Vaccinia Virus (VV) through the tail vein. For the anti-CTLA4 group, 100 μg of anti-CTLA4 antibody was injected intraperitoneally at days 0, 3 and 6. For the combination group, anti-CTLA4 antibody doses were administrated at days 4, 7 and 10 after virus injection. Tumor volumes were measured and relative tumor volume +SE of the 12–15 mice/group is plotted. (b) Combination therapy increases cytotoxic T cells recognizing tumor antigens. Cellular immune responses to tumor cells was evaluated by IFN-γ ELISpot assay. At day 11 post-virus administration spleens were harvested from Balb/c mice bearing Renca tumors and treated as in (a). Splenocytes were evaluated for CTLs recognizing Renca cells. Values of individual mice and means ± SEM are depicted. (*P<0.05 compared with PBS group; φ P<0.05 compared with VV group; # P<0.05 compared with anti-CTLA4 group)