Optimal therapeutic strategy using antigen-containing liposomes selectively delivered to antigen-presenting cells

Cancer Sci. 2019 Mar;110(3):875-887. doi: 10.1111/cas.13934. Epub 2019 Feb 16.

Abstract

Recent immunotherapies have shown clinical success. In particular, vaccines based on particulate antigen (Ag) are expected to be implemented based on their efficacy. In the current study, we describe a strategy entailing Ag-encapsulating PEG-modified liposomes (PGL-Ag) as antigen protein delivery devices and show that the success of the liposome depends on the antigen-presenting cell (APC) capacity; after administration of PGL-Ag, dendritic cells (DCs) in particular take up the Ag and subsequently prime T cells. For the generation of antitumor T cell responses in the lymphoid tissues, the function of encapsulated Ag-capturing DCs in vivo could be a biomarker. We next designed a prime-boost strategy to enhance the antitumor effects of the PGL-Ag. In the tumor sites, we show that Ag retention in nanoparticle-capturing DCs promotes a robust antitumor response. Thus, this efficient particulate Ag-based host antigen-presenting cell delivery strategy provides a bridge between innate and adaptive immune response and offers a novel therapeutic option against tumor cells.

Keywords: adaptive immunity; dendritic cell; immunotherapy; nanoparticle; tumor microenvironment.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigens / immunology*
  • Biomarkers, Tumor / immunology
  • Cancer Vaccines / immunology
  • Cell Line, Tumor
  • Dendritic Cells / immunology
  • Drug Delivery Systems / methods
  • Liposomes / chemistry*
  • Lymphocytes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry
  • T-Lymphocytes / immunology

Substances

  • Antigens
  • Biomarkers, Tumor
  • Cancer Vaccines
  • Liposomes