Click‐Chemistry‐Mediated Cell Membrane Glycopolymer Engineering to Potentiate Dendritic Cell Vaccines

Abstract Dendritic cell vaccine (DCV) holds great potential in tumor immunotherapy owing to its potent ability in eliciting tumor‐specific immune responses. Aiming at engineering enhanced DCV, we report the first effort to construct a glycopolymer‐engineered DC vaccine (G‐DCV) via metabolicglycoengineering and copper‐free click‐chemistry. Model G‐DCV was prepared by firstly delivering tumor antigens, ovalbumin (OVA) into dendritic cells (DC) with fluoroalkane‐grafted polyethyleneimines, followed by conjugating glycopolymers with a terminal group of dibenzocyclooctyne (DBCO) onto dendritic cells. Compared to unmodified DCV, our G‐DCV could induce stronger T cell activation due to the enhanced adhesion between DCs and T cells. Notably, such G‐DCV could more effectively inhibit the growth of the mouse B16‐OVA (expressing OVA antigen) tumor model after adoptive transfer. Moreover, by combination with an immune checkpoint inhibitor, G‐DCV showed further increased anti‐tumor effects in treating different tumor models. Thus, our work provides a novel strategy to enhance the therapeutic effectiveness of DC vaccines.