Dendritic cell-targeted delivery of antigens using extracellular vesicles for anti-cancer immunotherapy

Cell Prolif. 2024 Jul;57(7):e13622. doi: 10.1111/cpr.13622. Epub 2024 Mar 20.

Abstract

Neoantigen delivery using extracellular vesicles (EVs) has gained extensive interest in recent years. EVs derived from tumour cells or immune cells have been used to deliver tumour antigens or antitumor stimulation signals. However, potential DNA contamination from the host cell and the cost of large-scale EV production hinder their therapeutic applications in clinical settings. Here, we develop an antigen delivery platform for cancer vaccines from red blood cell-derived EVs (RBCEVs) targeting splenic DEC-205+ dendritic cells (DCs) to boost the antitumor effect. By loading ovalbumin (OVA) protein onto RBCEVs and delivering the protein to DCs, we were able to stimulate and present antigenic OVA peptide onto major histocompatibility complex (MHC) class I, subsequently priming activated antigen-reactive T cells. Importantly, targeted delivery of OVA using RBCEVs engineered with anti-DEC-205 antibody robustly enhanced antigen presentation of DCs and T cell activation. This platform is potentially useful for producing personalised cancer vaccines in clinical settings.

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens, Neoplasm* / immunology
  • Cancer Vaccines* / administration & dosage
  • Cancer Vaccines* / immunology
  • Dendritic Cells* / immunology
  • Dendritic Cells* / metabolism
  • Extracellular Vesicles* / immunology
  • Extracellular Vesicles* / metabolism
  • Humans
  • Immunotherapy* / methods
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Ovalbumin* / administration & dosage
  • Ovalbumin* / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Cancer Vaccines
  • Ovalbumin
  • Antigens, Neoplasm