Figure 7.

Systemic antitumor and anti-metastatic effects of the combined therapy. A. Comparison of different checkpoint antibodies in combination with 14.18-IL2 IC against B78 melanoma. C57BL/6 mice were injected s.c. with 2×10⁶ B78 cells. 14.18-IL2 IC (5 mcg/mouse) was injected i.t. on days 12–16. Various checkpoint antibodies (200 mcg/mouse) were injected i.p. on days 12,14,16,19,21 and 23. B,C. B78 melanoma cells (2×10⁶) were injected s.c. into the right and left sides of the abdomen on day 0. Each tumor on the left was injected with CpG (25 mcg) on days 12,14,16 and with14.18-IL2 IC (25 mcg) on days 12–16. These treatments were given in combination with i.p. injections of anti-CD40 (500 mcg) on day 9 and anti-CTLA-4, IgG2a (200 mcg) on days 12,14,16,19,21,23. The results are shown as means ± SEM of volumes of the left side (treated) (B) and right side (untreated) (C) tumors. D-F: C57BL/6 mice were injected s.c. with 2×10⁶ B78 melanoma cells (day 0) and i.v. with 1×10⁵ B16-F10 melanoma cells (day 1). Mice were treated with anti-CD40 (0.5 mg) i.p. on day 8, with CpG (25 mcg) i.t. on days 11,13,15, with 14.18-IL2 IC (25 mcg) i.t. on days 11–15, and with anti-CTLA-4 IgG2a (200 mcg) i.p. on days 11,13,15,18,20,21. The results are shown as means ± SEM of s.c. tumor volumes (D) and survival (E) of 5 mice per group. Lung photographs taken on day 32 from a separate identical experiment are shown, contrasting visable metastases in control vs. treated mice (F).