Cancer immunotherapy is a new generation cancer treatment that employs therapeutic agents such as antibodies, cells, peptides, and nucleic acids to activate immune cells to target cancer cells and eliminate them. Our interest has focused on the polyneoepitope-encoding RNA vaccine. Neoepitopes are mutated peptides restricted to only cancer cells, and are bound to major histocompatibility complex (MHC) molecules on the cell surface to be recognized by T-cells. Polyneoepitopes have been shown to be good targets against cancer in mouse models and human trials, being clinically feasible, safe, and able to induce anti-tumor activity and immunity. The drawback to this vaccine is the instability of the RNA molecule; therefore, patients have to receive multiple injections over the duration of their treatment. Here, we present a solution by exploiting the self-replicating ability of the RNA genome of dengue virus (DENV) to allow RNA to maintain its population in host cells. To provide a proof-of-concept study, we designed and constructed a new RNA vaccine containing the untranslated regions and non-structural protein (NS) genes from DENV, which are linked to a polyneoepitopes from MC38, a murine colon adenocarcinoma. We have almost completed the cloning processes using the In-Fusion cloning technique. Future work includes synthesis of replicon RNA in vitro and its transfection into murine macrophages to confirm self-replication and neoepitope presentation via Western blot and mass spectrometry. Feasibility of this study allows for the replicon RNA to be further examined in mouse models to potentiate a better alternative for cancer immunotherapy in the future.