In both the B78 melanoma model (data not shown) and the 9464D-GD2 model (Additional file 1: Figure S1), full combined treatment with RT, IT-IC, anti-CTLA-4, and anti-CD40/CpG was more effective than different double and triple combinations of these agents (with anti-CD40 and CpG being considered as one synergistic treatment activating innate immunity), where in both tumor models only full combined treatment resulted either in complete tumor regression in some mice or in the strongest tumor growth suppression. Here, CD40 is linked to melanoma.