PMID- 26083554
OWN - NLM
STAT- MEDLINE
DCOM- 20160420
LR  - 20181113
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Linking)
VI  - 135
IP  - 11
DP  - 2015 Nov
TI  - In situ Delivery of Tumor Antigen- and Adjuvant-Loaded Liposomes Boosts 
      Antigen-Specific T-Cell Responses by Human Dermal Dendritic Cells.
PG  - 2697-2704
LID - S0022-202X(15)41856-1 [pii]
LID - 10.1038/jid.2015.226 [doi]
AB  - 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.
FAU - Boks, Martine A
AU  - Boks MA
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical Center 
      (VUmc), Amsterdam, The Netherlands.
FAU - Bruijns, Sven C M
AU  - Bruijns SCM
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical Center 
      (VUmc), Amsterdam, The Netherlands.
FAU - Ambrosini, Martino
AU  - Ambrosini M
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical Center 
      (VUmc), Amsterdam, The Netherlands.
FAU - Kalay, Hakan
AU  - Kalay H
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical Center 
      (VUmc), Amsterdam, The Netherlands.
FAU - van Bloois, Louis
AU  - van Bloois L
AD  - Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences 
      (UIPS), Utrecht University, Utrecht, The Netherlands.
FAU - Storm, Gert
AU  - Storm G
AD  - 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.
FAU - Gruijl, Tanja de
AU  - Gruijl T
AD  - Department of Medical Oncology, VU University Medical Center (VUmc), Amsterdam, 
      The Netherlands.
FAU - van Kooyk, Yvette
AU  - van Kooyk Y
AD  - Department of Molecular Cell Biology and Immunology, VU University Medical Center 
      (VUmc), Amsterdam, The Netherlands. Electronic address: y.vankooyk@vumc.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150617
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Liposomes)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Antigen Presentation/*immunology
MH  - Antigens, Neoplasm/*pharmacology
MH  - Biopsy, Needle
MH  - CD8-Positive T-Lymphocytes/drug effects/immunology
MH  - Cancer Vaccines/pharmacology
MH  - Cells, Cultured
MH  - Cross-Priming
MH  - Dendritic Cells/*drug effects/*immunology
MH  - Flow Cytometry
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunotherapy/methods
MH  - Liposomes/pharmacology
MH  - Skin/cytology/*drug effects/pathology
MH  - Toll-Like Receptors/immunology
EDAT- 2015/06/18 06:00
MHDA- 2016/04/21 06:00
CRDT- 2015/06/18 06:00
PHST- 2015/03/10 00:00 [received]
PHST- 2015/05/21 00:00 [revised]
PHST- 2015/06/04 00:00 [accepted]
PHST- 2015/06/18 06:00 [entrez]
PHST- 2015/06/18 06:00 [pubmed]
PHST- 2016/04/21 06:00 [medline]
AID - S0022-202X(15)41856-1 [pii]
AID - 10.1038/jid.2015.226 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2015 Nov;135(11):2697-2704. doi: 10.1038/jid.2015.226. Epub 
      2015 Jun 17.