A Synthetic MUC1 Anticancer Vaccine Containing Mannose Ligands for Targeting Macrophages and Dendritic Cells

A MUC1 anticancer vaccine equipped with covalently linked divalent mannose ligands was found to improve the antigen uptake and presentation by targeting mannose‐receptor‐positive macrophages and dendritic cells. It induced much stronger specific IgG immune responses in mice than the non‐mannosylated reference vaccine. Mannose coupling also led to increased numbers of macrophages, dendritic cells, and CD4+ T cells in the local lymph organs. Comparison of di‐ and tetravalent mannose ligands revealed an increased binding of the tetravalent version, suggesting that higher valency improves binding to the mannose receptor. The mannose‐coupled vaccine and the non‐mannosylated reference vaccine induced IgG antibodies that exhibited similar binding to human breast tumor cells. Mind your B and T cells: MUC1 glycopeptide antitumor vaccines linked to mannose ligands of mannose receptors on macrophages and dendritic cells induce much stronger specific IgG responses than analogous non‐mannosylated reference vaccines due to inclusion of the innate immune system in B cell activation. Thus, both the adapted and innate immune systems potentiate the immune response against the tumor‐associated MUC1 antigen.