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

作者：Glaffig Markus; Stergiou Natascha; Hartmann Sebastian; Schmitt Edgar; Kunz Horst^*

来源：ChemMedChem, 2018, 13(1): 25-29.

DOI：10.1002/cmdc.201700646

• antitumor vaccines
• cancer immunotherapy
• macrophage activation
• mannose receptors
• MUC1 glycopeptide

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.

• 出版日期2018-1-8