PMID- 25656175
OWN - NLM
STAT- MEDLINE
DCOM- 20160309
LR  - 20150324
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 203
DP  - 2015 Apr 10
TI  - Cross-presentation through langerin and DC-SIGN targeting requires different 
      formulations of glycan-modified antigens.
PG  - 67-76
LID - S0168-3659(15)00090-5 [pii]
LID - 10.1016/j.jconrel.2015.01.040 [doi]
AB  - Dendritic cells (DCs) and Langerhans cells (LC) are professional antigen 
      presenting cells (APCs) that initiate humoral and cellular immune responses. 
      Targeted delivery of antigen towards DC- or LC-specific receptors enhances 
      vaccine efficacy. In this study, we compared the efficiency of glycan-based 
      antigen targeting to both the human DC-specific C-type lectin receptor (CLR) 
      DC-SIGN and the LC-specific CLR langerin. Since DC-SIGN and langerin are able to 
      recognize the difucosylated oligosaccharide Lewis Y (Le(Y)), we prepared 
      neoglycoconjugates bearing this glycan epitope to allow targeting of both 
      lectins. Le(Y)-modified liposomes, with an approximate diameter of 200nm, were 
      significantly endocytosed by DC-SIGN(+) DCs and mediated efficient antigen 
      presentation to CD4(+) and CD8(+) T cells. Surprisingly, although langerin bound 
      to Le(Y)-modified liposomes, LCs exposed to Le(Y)-modified liposomes could not 
      endocytose liposomes nor mediate antigen presentation to T cells. However, LCs 
      mediated an enhanced cross-presentation when antigen was delivered through 
      langerin using Le(Y)-modified synthetic long peptides. In contrast, 
      Le(Y)-modified synthetic long peptides were recognized by DC-SIGN, but did not 
      trigger antigen internalization nor antigen cross-presentation. These data 
      demonstrate that langerin and DC-SIGN have different size requirements for 
      antigen uptake. Although using glycans remains an interesting option in the 
      design of anti-cancer vaccines targeting multiple CLRs, aspects such as molecule 
      size and conformation need to be taken in consideration.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Fehres, Cynthia M
AU  - Fehres CM
AD  - Department of Molecular Cell Biology and Immunology, VUmc, Amsterdam, The 
      Netherlands.
FAU - Kalay, Hakan
AU  - Kalay H
AD  - Department of Molecular Cell Biology and Immunology, VUmc, Amsterdam, The 
      Netherlands.
FAU - Bruijns, Sven C M
AU  - Bruijns SC
AD  - Department of Molecular Cell Biology and Immunology, VUmc, Amsterdam, The 
      Netherlands.
FAU - Musaafir, Sara A M
AU  - Musaafir SA
AD  - Department of Molecular Cell Biology and Immunology, VUmc, Amsterdam, The 
      Netherlands.
FAU - Ambrosini, Martino
AU  - Ambrosini M
AD  - Department of Molecular Cell Biology and Immunology, 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 - van Vliet, Sandra J
AU  - van Vliet SJ
AD  - Department of Molecular Cell Biology and Immunology, VUmc, Amsterdam, 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 - Garcia-Vallejo, Juan J
AU  - Garcia-Vallejo JJ
AD  - Department of Molecular Cell Biology and Immunology, VUmc, Amsterdam, The 
      Netherlands.
FAU - van Kooyk, Yvette
AU  - van Kooyk Y
AD  - Department of Molecular Cell Biology and Immunology, VUmc, Amsterdam, The 
      Netherlands. Electronic address: y.vankooyk@vumc.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150202
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Antigens)
RN  - 0 (Antigens, CD)
RN  - 0 (CD207 protein, human)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Glycoconjugates)
RN  - 0 (Glycosphingolipids)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Liposomes)
RN  - 0 (Mannose-Binding Lectins)
RN  - 0 (Peptides)
RN  - 0 (Polysaccharides)
RN  - 0 (Receptors, Cell Surface)
RN  - 88161-63-1 (Y glycolipid)
SB  - IM
MH  - Amino Acid Sequence
MH  - Antigen Presentation
MH  - Antigens/chemistry/*immunology
MH  - Antigens, CD/*immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cancer Vaccines/administration & dosage/immunology
MH  - Carbohydrate Sequence
MH  - Cell Adhesion Molecules/*immunology
MH  - *Cross-Priming
MH  - Dendritic Cells/immunology
MH  - Drug Delivery Systems
MH  - Glycoconjugates/chemistry/*immunology
MH  - Glycosphingolipids/chemistry/immunology
MH  - Humans
MH  - Langerhans Cells/immunology
MH  - Lectins, C-Type/*immunology
MH  - Liposomes/chemistry/*immunology
MH  - Mannose-Binding Lectins/*immunology
MH  - Molecular Sequence Data
MH  - Peptides/chemistry/immunology
MH  - Polysaccharides/chemistry/*immunology
MH  - Receptors, Cell Surface/*immunology
OTO - NOTNLM
OT  - Anti-tumor vaccination
OT  - DC-SIGN
OT  - Glycans
OT  - Human dendritic cells
OT  - Langerin
OT  - Liposomes
EDAT- 2015/02/07 06:00
MHDA- 2016/03/10 06:00
CRDT- 2015/02/07 06:00
PHST- 2014/11/21 00:00 [received]
PHST- 2015/01/29 00:00 [revised]
PHST- 2015/01/30 00:00 [accepted]
PHST- 2015/02/07 06:00 [entrez]
PHST- 2015/02/07 06:00 [pubmed]
PHST- 2016/03/10 06:00 [medline]
AID - S0168-3659(15)00090-5 [pii]
AID - 10.1016/j.jconrel.2015.01.040 [doi]
PST - ppublish
SO  - J Control Release. 2015 Apr 10;203:67-76. doi: 10.1016/j.jconrel.2015.01.040. 
      Epub 2015 Feb 2.