Cancer immunotherapy in today’s clinical practice consists mostly of immune checkpoint inhibitors, which act by reactivating exhausted T-cells in and around the tumor. These drugs can produce considerable systemic side effects, and a large proportion of tumors are immune “cold” and lack T-cells, precluding any therapeutic efficacy. We have observed that vaccination using dendritic cells activated by a TLR4 ligand and interferon gamma can reverse the cold tumor phenotype and lead to massive intratumoral killer T-cell infiltration. In this project we will develop an mRNA-based artificial construct that can re-ignite anti-cancer immune responses while also avoiding toxic collateral effects. This approach can be implemented both as part of liposomal mRNA vaccine, as well as integrated into our exisiting dendritic cell therapy program.