Vaccination with trifunctional nanoparticles that address CD8+ dendritic cells inhibits growth of established melanoma

Nanomedicine (Lond). 2016 Oct;11(20):2647-2662. doi: 10.2217/nnm-2016-0174. Epub 2016 Sep 15.

Abstract

Aim: We wanted to assess the potency of a trifunctional nanoparticle (NP) that targeted and activated CD8+ dendritic cells (DC) and delivered an antigen to induce antitumor responses.

Materials & methods: The DC targeting and activating properties of ferrous NPs conjugated with immunostimulatory CpG-oligonucleotides, anti-DEC205 antibody and ovalbumin (OVA) as a model antigen to induce antigen-specific T-cell responses and antitumor responses were analyzed.

Results: OVA-loaded NP conjugated with immunostimulatory CpG-oligonucleotides and anti-DEC205 antibody efficiently targeted and activated CD8+ DC in vivo, and induced strong OVA-specific T-cell activation. Vaccination of B16/OVA tumor-burdened mice with this NP formulation resulted in tumor growth arrest.

Conclusion: CD8+ DC-targeting trifunctional nanocarriers bear significant potential for antitumor immunotherapy.

Keywords: CTL; CpG; DEC205; IFN-γ; MDSC; TNF-α; dendritic cell; nanoparticles; targeting; tumor therapy.

MeSH terms

  • Animals
  • Antibodies / chemistry
  • Antibodies / immunology
  • Antigens, CD / immunology
  • CD8 Antigens / metabolism*
  • Cell Proliferation
  • CpG Islands
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dextrans / chemistry
  • Fluorescent Dyes / chemistry
  • Humans
  • Immunotherapy
  • Lectins, C-Type / immunology
  • Lymphocyte Activation
  • Magnetite Nanoparticles / chemistry*
  • Magnetite Nanoparticles / therapeutic use
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy*
  • Mice, Inbred C57BL
  • Minor Histocompatibility Antigens / immunology
  • Oligonucleotides / chemistry
  • Oligonucleotides / immunology*
  • Ovalbumin / immunology*
  • Receptors, Cell Surface / immunology
  • Surface Properties
  • Tumor Burden
  • Vaccination

Substances

  • Antibodies
  • Antigens, CD
  • CD8 Antigens
  • DEC-205 receptor
  • Dextrans
  • Fluorescent Dyes
  • Lectins, C-Type
  • Magnetite Nanoparticles
  • Minor Histocompatibility Antigens
  • Oligonucleotides
  • Receptors, Cell Surface
  • Ovalbumin