Figure 1. Treatment with agonistic anti-4-1BB and blocking anti-CTLA-4 delays tumor growth only in mice challenged with tumor cells expressing a strong foreign antigen.

Mice (n = 8–10 mice/group) were inoculated s.c. in the right flank with 10⁶ melanoma cells at day 0 and antibodies were administered i.p. as described. A: a) Mice vaccinated with 2×10⁷ IFU Ad-IiGP in the right hind footpad 5 days post B16.F10 inoculation (pt). b) As in a, plus treatment with 200 µg anti-4-1BB at days 9 and 12 pt. c) As in a, plus treatment with 100 µg anti-CTLA-4 at day 5 and 50 µg anti-CTLA-4 at days 7 and 9 pt. d) As in a, plus treatment with anti-4-1BB and anti-CTLA-4 as in b and c, respectively. e) B16.F10 tumor cells, no vaccination, antibody treatment as in d. f) B16.F10 tumor cells, no treatment. P-values: e vs. f <0.0001; a vs. d = 0.0220; d vs. e = 0.9400. B: Solid lines indicate mice challenged with B16.F10-GP cells; dashed lines indicate mice challenged with B16.F10 cells. Grey lines indicate mice that did not receive any treatment. Black lines indicate mice treated i.p. with 200 µg anti-4-1BB at days 9 and 12 plus 100 µg anti-CTLA-4 at days 5 and 50 µg anti-CTLA-4 at days 7 and 9 pt. Mortality of tumor bearing mice as a function of time. P-values: a vs. b <0.0001; a vs. d = 1.0000; b vs. d = 0.0003; c vs. d = 0.1850 C: Tumor volumes as a function of time; data are presented as mean ± SEM. P-values: a vs. b <0.0001.