title: Vaccination with trifunctional nanoparticles that address CD8+dendritic cells inhibits growth of established melanoma.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  CD8+DC-targeting trifunctional nanocarriers bear significant potential for antitumor immunotherapy.
authors.affiliation: Department of Dermatology, University Medical Center Mainz, Germany.
authors.forename: Limei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Miltenyi Biotec, Bergisch Gladbach, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Krauthäuser
authors.affiliation: Institute for Physical Chemistry, Johannes Gutenberg-University Mainz, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Fischer
authors.affiliation: Department of Dermatology, University Medical Center Mainz, Germany.
authors.forename: Dominika
authors.initials: D
authors.lastname: Hobernik
authors.affiliation: Department of Internal Medicine III, Division of Translational & Experimental Oncology, University Medical Center Mainz, Germany.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Abassi
authors.affiliation: Miltenyi Biotec, Bergisch Gladbach, Germany.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Dzionek
authors.affiliation: Institute for Molecular Medicine, University Medical Center Mainz, Germany.
authors.forename: Alexej
authors.initials: A
authors.lastname: Nikolaev
authors.affiliation: Department of Dermatology, University Medical Center Mainz, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Voltz
authors.affiliation: TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University gGmbH, Mainz, Germany.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Diken
authors.affiliation: Department of Dermatology, University Medical Center Mainz, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Krummen
authors.affiliation: Department of Dermatology, University Medical Center Mainz, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Montermann
authors.affiliation: Department of Dermatology, University Medical Center Mainz, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Tubbe
authors.affiliation: Imaging Core Facility, University Medical Center Mainz, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Lorenz
authors.affiliation: Imaging Core Facility, University Medical Center Mainz, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Strand
authors.affiliation: Institute of Immunology, University Medical Center Mainz, Germany.
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Schild
authors.affiliation: Department of Dermatology, University Medical Center Mainz, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Grabbe
authors.affiliation: Department of Dermatology, University Medical Center Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bros
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D016827:CD8 Antigens / Q000378:metabolism*; D049109:Cell Proliferation; D018899:CpG Islands; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007167:Immunotherapy; D037181:Lectins, C-Type / Q000276:immunology; D008213:Lymphocyte Activation; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D009841:Oligonucleotides / Q000737:chemistry / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology; D013499:Surface Properties; D047368:Tumor Burden; D014611:Vaccination
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D016827:CD8 Antigens; C093569:DEC-205 receptor; D003911:Dextrans; D005456:Fluorescent Dyes; D037181:Lectins, C-Type; D058185:Magnetite Nanoparticles; D015778:Minor Histocompatibility Antigens; D009841:Oligonucleotides; D011956:Receptors, Cell Surface; D010047:Ovalbumin
keywords: CTL; CpG; DEC205; IFN-γ; MDSC; TNF-α; dendritic cell; nanoparticles; targeting; tumor therapy