No advantage of cell-penetrating peptides over receptor-specific antibodies in targeting antigen to human dendritic cells for cross-presentation.

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Publication year
2008Source
Journal of Immunology, 180, 11, (2008), pp. 7687-96ISSN
Publication type
Article / Letter to editor

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Organization
Tumorimmunology
Nuclear Medicine
Journal title
Journal of Immunology
Volume
vol. 180
Issue
iss. 11
Page start
p. 7687
Page end
p. 96
Subject
IGMD 1: Functional imaging; N4i 1: Pathogenesis and modulation of inflammation; NCMLS 1: Immunity, infection and tissue repair; NCMLS 2: Immune Regulation; NCMLS 3: Tissue engineering and pathology; ONCOL 3: Translational research; UMCN 1.1: Functional Imaging; UMCN 1.4: Immunotherapy, gene therapy and transplantationAbstract
Induction of CTL responses by dendritic cell (DC)-based vaccines requires efficient DC-loading strategies for class I Ags. Coupling Ags to cell-penetrating peptides (CPPs) or receptor-specific Abs improves Ag loading of DCs. In contrast to CPPs, receptor-specific Abs deliver conjugated Ags to DCs with high specificity, which is advantageous for in vivo strategies. It has, however, been speculated that CPPs facilitate uptake and endosomal escape of conjugated Ags, which would potently enhance cross-presentation. In this study, we directly compare the in vitro targeting efficiency of a humanized D1 Ab directed against the human DC surface receptor DC-SIGN hD1 to that of three CPPs. The three CPPs colocalized within endosomes when targeted to human monocyte-derived DCs simultaneously, whereas hD1 was present in a different set of endosomes. However, within 75 min after uptake CPPs and hD1 colocalized extensively within the lysosomal compartment. Ab-mediated targeting of class I-restricted peptides to DC-SIGN enhanced cross-presentation of the peptides, while only one of the CPPs enhanced peptide presentation. This CPP and hD1 enhanced cross-presentation with equal efficiencies. Thus, we found no evidence of CPP specifically favoring the delivery of conjugated Ag to the DC class I presentation pathway. Given the specificity with which Abs recognize their targets, this favors the use of DC receptor-specific Abs for in vivo vaccination strategies.
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- Academic publications [227613]
- Electronic publications [107286]
- Faculty of Medical Sciences [86193]
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