Development of a whole cell vaccine to activate dendritic cells using polyvalent CpG

To promote the co-delivery of antigens and adjuvants into antigen-presenting cells (APCs) is vital for whole cell vaccine-based immunotherapy. The purpose of this work was to design a novel whole cell vaccine by functionalizing the surface of cancer cells with polyvalent CpG (PCpG) oligodeoxynucleotides through nucleic acid assembly and hybridization. The PCpG-engineered vaccine was successfully prepared with a high CpG loading (3-fold increase) on the cell surface. The vaccine could be internalized efficiently by dendritic cells (DCs), enhancing the maturation of DCs with the expression of antigens and cytokines at a higher level compared to the native vaccine. In a mouse model, locally administered PCpG-engineered whole cell vaccines provoked potent immune stimulation in terms of antigen expression of DCs and T cells in lymphoid tissues. Eventually, tumor growth and lung metastasis were inhibited efficiently. Notably, while we demonstrated the display of CpG, many other ligands can be used as substitutes of CpG. Therefore, this work opens a new pathway to develop a whole cell vaccine.