title: In situ Delivery of Tumor Antigen- and Adjuvant-Loaded Liposomes Boosts Antigen-Specific T-Cell Responses by Human Dermal Dendritic Cells.
abstract: Dendritic cells (DCs) have an important role in tumor control via the induction of tumor-specific T-cell responses and are therefore an ideal target for immunotherapy. The human skin is an attractive site for tumor vaccination as it contains various DC subsets. The simultaneous delivery of tumor antigen with an adjuvant is beneficial for cross-presentation and the induction of tumor-specific T-cell responses. We therefore developed liposomes that contain the melanoma-associated antigen glycoprotein 100280-288 peptide and Toll-like receptor 4 (TLR4) ligand monophosphoryl lipid A (MPLA) as adjuvant. These liposomes are efficiently taken up by monocyte-derived DCs, and antigen presentation to CD8(+) T cells was significantly higher with MPLA-modified liposomes as compared with non-modified liposomes or the co-administration of soluble MPLA. We used a human skin explant model to evaluate the efficiency of intradermal delivery of liposomes. Liposomes were efficiently taken up by CD1a(+) and especially CD14(+) dermal DCs. Induction of CD8(+) T-cell responses by emigrated dermal DCs was significantly higher when MPLA was incorporated into the liposomes as compared with non-modified liposomes or co-administration of soluble MPLA. Thus, the modification of antigen-carrying liposomes with TLR ligand MPLA significantly enhances tumor-specific T-cell responses by dermal DCs and is an attractive vaccination strategy in human skin.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center (VUmc), Amsterdam, The Netherlands.
authors.forename: Martine A
authors.initials: MA
authors.lastname: Boks
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center (VUmc), Amsterdam, The Netherlands.
authors.forename: Sven C M
authors.initials: SCM
authors.lastname: Bruijns
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center (VUmc), Amsterdam, The Netherlands.
authors.forename: Martino
authors.initials: M
authors.lastname: Ambrosini
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center (VUmc), Amsterdam, The Netherlands.
authors.forename: Hakan
authors.initials: H
authors.lastname: Kalay
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: van Bloois
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands; MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.affiliation: Department of Medical Oncology, VU University Medical Center (VUmc), Amsterdam, The Netherlands.
authors.forename: Tanja de
authors.initials: T
authors.lastname: Gruijl
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center (VUmc), Amsterdam, The Netherlands. Electronic address: y.vankooyk@vumc.nl.
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000494:pharmacology*; D001707:Biopsy, Needle; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D019496:Cancer Vaccines / Q000494:pharmacology; D002478:Cells, Cultured; D045142:Cross-Priming; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D008081:Liposomes / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D008081:Liposomes; D051193:Toll-Like Receptors