Abstract
Dendritic cell (DC)-based immunotherapy has been hampered by the lack of suitable methods for antigen delivery. Here, we use biodegradable poly(D,L-lactide-co-glycolide) microspheres (PLGA-MS) as carriers of peptides and proteins for antigen delivery to human monocyte-derived DC (MoDC). Compared to soluble proteins, MHC classes I and II-restricted presentation of PLGA-MS-encapsulated proteins and peptides by MoDC was markedly prolonged and proteins were presented 50-fold more efficiently on class I molecules. The vaccination of mice with DC loaded with PLGA-MS-encapsulated proteins raised strong and persisting cytotoxic T cell responses. In conclusion, antigen delivery via PLGA-MS markedly enhanced the duration of antigen presentation by human MoDC and the potency of DC-based vaccination.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation
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Cell Line
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Cytotoxicity Tests, Immunologic
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Delayed-Action Preparations
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Dendritic Cells / immunology*
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Humans
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Lactic Acid*
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Mice
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Mice, Inbred C57BL
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Microspheres*
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Peptide Fragments / administration & dosage
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Peptides / administration & dosage
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Peptides / immunology*
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Peptides / metabolism
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Polyglycolic Acid*
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Polylactic Acid-Polyglycolic Acid Copolymer
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Polymers*
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Proteins / administration & dosage
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Proteins / immunology*
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Proteins / metabolism
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T-Lymphocytes, Cytotoxic / immunology
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Tetanus Toxoid / administration & dosage
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Tetanus Toxoid / immunology
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Tetanus Toxoid / metabolism
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Vaccination / methods
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Viral Matrix Proteins / administration & dosage
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Viral Matrix Proteins / immunology
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Viral Matrix Proteins / metabolism
Substances
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Delayed-Action Preparations
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Peptide Fragments
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Peptides
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Polymers
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Proteins
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Tetanus Toxoid
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Viral Matrix Proteins
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influenza matrix peptide (58-66)
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Polylactic Acid-Polyglycolic Acid Copolymer
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Polyglycolic Acid
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Lactic Acid