Metabolic labelling of cancer cells with glycodendrimers stimulate immune-mediated cytotoxicity

Abstract

The recruitment of antibody naturally present in human blood stream at the surface of cancer cells have been proved a promising immunotherapeutic strategy to fight cancer. Antibody recruiting molecules (ARMs) combining tumor and antibody binding modules have been developed for this purpose, however the formation of the interacting complex with both antibody and cell is difficult to optimize to stimulate immune-mediated cytotoxicity. To circumvent this limitation, we report herein a more direct approach combining cell metabolism of azido-sugar and bio-orthogonal click chemistry to conjugate at the cell glycocalyx structurally well-defined glycodendrimers as antibody binding module (ABM). We demonstrate that this strategy allows not only the recruitment of natural antibody at the surface of isolated cells or solid tumor models but also activate a cytotoxic response with human serum as unique source of immune effectors.