As innate agonists of both TLR and the Stimulator of Interferon Genes pathways are now being administered to patients both intra-tumorally as well as systemically, we investigated the impact of route of delivery on the efficacy of ODN1826 with or without anti-CTLA-4 or anti-PD-1 on the progression of bi-laterally implanted B16-F10 parental melanoma. The gene discussed is CTLA4; the disease is melanoma.