Targeting C-type lectins on dendritic cells using carbohydrate-analogs for the specific delivery of tumor vaccines

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The tumor microenvironment is immune suppressive and as a consequence immune cells become tolerant over tumor cells. In order to develop anti-cancer vaccines that activate the immune system against the tumor, it is essential to overcome this tolerance. Dendritic cells are the most important antigen presenting cells in the body and orchestrate the interplay between various immune cells. Therefore, dendritic cells are attractive targets for the activation of the immune response against cancer. Certain C-type lectins are uniquely expressed on the cell surface of dendritic cells. Thus in principle, these receptors are ideal targets for delivery of immunomodulatory agents to dendritic cells. Natural carbohydrate ligands of these lectin receptors resemble well-suited precursors to develop analogs for specific targeting. Biophysical techniques will be combined with computer-aided design of specific ligands that are then chemically synthesized. Finally, these ligands are coupled to liposomes, which are long-lived stealth vehicles that are able to carry tumor antigens as cargo to dendritic cells. The success of this design process is evaluated in three stages. First, the liposomal vehicles will be tested for binding to mammalian model cells expressing specific C-type lectins. Then, isolated immune cells will serve to analyze the efficient delivery of tumor antigens in vitro. Finally, the targeted liposomes are applied in vivo to ensure effective delivery and activation in a murine cancer model.