Numerous nucleic acid sensor agonists are being trialed for use in cancer immunotherapy, with TLR and STING agonists among the most studied. When administered systemically, however, these small-molecule agonists often have systemic side-effects and are cleared before reaching their target. In this thesis, we explored two approaches to this problem. First, we developed a pH-responsive nanoparticle delivery system that improved the pharmacokinetics of the TLR7 agonist resiquimod. This enhanced local immune activation in mice while reducing systemic exposure, thus offering a promising platform for adjuvant therapies and cancer vaccines. Second, we assessed combinations of agonists with regard to their potency in enhancing DC activation and their impact on cytotoxic T-cell responses. We showed that while the combination of TLR and STING agonists efficiently and synergistically upregulated DC activation, it also upregulated tolerogenic and apoptosis-inducing factors, causing rapid death in co-cultured cytotoxic T cells. The selection of agonists thus requires careful evaluation.