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

Angew Chem Int Ed Engl. 2024 Jan 8;63(2):e202315782. doi: 10.1002/anie.202315782. Epub 2023 Dec 8.

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.

Keywords: Cell Surface Modification; Dendritic Cell Vaccines; Polymer; T-Cell Activation; Tumor Immunotherapy.

MeSH terms

  • Animals
  • Antigens, Neoplasm
  • Cell Membrane
  • Dendritic Cells / metabolism
  • Mice
  • Neoplasms* / metabolism
  • Ovalbumin
  • T-Lymphocytes
  • Vaccines*

Substances

  • Antigens, Neoplasm
  • Ovalbumin
  • Vaccines