CircRNA-loaded DC vaccine in combination with low-dose gemcitabine induced potent anti-tumor immunity in pancreatic cancer model.

Although promising, dendritic cell (DC) vaccines may not suffice to fully inhibit tumor progression alone, mainly due to the short expression time of the antigen in DC vaccines, immunosuppressive tumor microenvironment, and tumor antigenic modulation. Overcoming the limitations of DC vaccines is expected to further enhance their anti-tumor effects. In this study, we constructed a circRNA-loaded DC vaccine utilizing the inherent stability of circular RNA to enhance the expression level and duration of the antigen within the DC vaccine. Meanwhile we combined it with gemcitabine and validated their therapeutic efficacy in the Panc02 tumor model. We found that the use of DC vaccine alone can reach a tumor inhibition rate of 69%, and the effect was further enhanced when combined with gemcitabine, reaching a tumor inhibition rate of 89%. The combined treatment achieved a synergistic effect, which not only reduced immunosuppressive Tregs but also induced immunogenic cell death, leading to antigen spreading and reducing immune evasion caused by tumor antigenic modulation. As a result, the survival of the mice was significantly prolonged. Our research provides a promising approach for the clinical treatment of pancreatic cancer.