Phenotype and functional analysis of human monocyte-derived dendritic cells loaded with biodegradable poly(lactide-co-glycolide) microspheres for immunotherapy

Lade...
Vorschaubild
Dateien
Waeckerle-Men_221328.pdf
Waeckerle-Men_221328.pdfGröße: 499.23 KBDownloads: 618
Datum
2004
Autor:innen
Waeckerle-Men, Ying
Scandella, Elke
Ludewig, Burkhard
Gillessen, Silke
Merkle, Hans P.
Gander, Bruno
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Open Access Green
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Zusammenfassung

Dendritic cells (DC) are increasingly explored as cellular vaccines for tumor immunotherapy. In most reported DC-based cancer vaccine trials, DC have been pulsed with soluble tumor antigen-derived peptide ligands of MHC molecules. Considering that the half-life of peptide/MHC complexes on the cell surface is relatively short and that soluble exogenous protein antigens cannot be efficiently processed via the MHC class I-processing pathway, the current vaccination procedure is not optimal for the induction of strong T cell responses aiming at tumor rejection. Recently, we have shown that antigen presentation can be prolonged when synthetic peptides were encapsulated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres (MS) for uptake by DC. In the present study, we investigated the phenotypic and functional consequences of MS uptake by human monocyte-derived dendritic cells (MoDC) in vitro. We found that immature MoDC that were prepared in serum free media suitable for clinical application were able to phagocytose high numbers of MS, while matured MoDC showed a reduced capacity for phagocytosis of MS. The ingestion of MS did not change the cell surface expression of CD80, CD83, CD86 and HLA-DR of immature and mature DC, suggesting that MS uptake did not induce DC maturation but that maturation by cytokines or LPS was unaltered in the presence of MS. Furthermore, MS-loaded mature MoDC expressed normal levels of the chemokine receptor CCR7 and migrated as efficiently towards CCL19 or CCL21 as unloaded MoDC. DC viability and the secretion of TNF-a and IL-12 was not significantly changed by MS loading. Taken together, our data indicate that PLGA-MS loading has no negative effects on the pivotal properties of MoDC in vitro. It should therefore be feasible to further develop this antigen loading strategy for clinical use in immunotherapy against viral infections and tumors.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Dendritic cells, Microspheres, Poly(lactide-co-glycolide), Immunotherapy, Antigen processing, Vaccine delivery
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690WAECKERLE-MEN, Ying, Elke SCANDELLA, Edith UETZ-VON ALLMEN, Burkhard LUDEWIG, Silke GILLESSEN, Hans P. MERKLE, Bruno GANDER, Marcus GRÖTTRUP, 2004. Phenotype and functional analysis of human monocyte-derived dendritic cells loaded with biodegradable poly(lactide-co-glycolide) microspheres for immunotherapy. In: Journal of Immunological Methods. 2004, 287(1-2), pp. 109-124. ISSN 0022-1759. eISSN 1872-7905. Available under: doi: 10.1016/j.jim.2004.01.010
BibTex
@article{WaeckerleMen2004-04Pheno-22132,
  year={2004},
  doi={10.1016/j.jim.2004.01.010},
  title={Phenotype and functional analysis of human monocyte-derived dendritic cells loaded with biodegradable poly(lactide-co-glycolide) microspheres for immunotherapy},
  number={1-2},
  volume={287},
  issn={0022-1759},
  journal={Journal of Immunological Methods},
  pages={109--124},
  author={Waeckerle-Men, Ying and Scandella, Elke and Uetz-von Allmen, Edith and Ludewig, Burkhard and Gillessen, Silke and Merkle, Hans P. and Gander, Bruno and Gröttrup, Marcus}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/22132">
    <dc:contributor>Scandella, Elke</dc:contributor>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-02-26T08:34:59Z</dcterms:available>
    <dc:contributor>Merkle, Hans P.</dc:contributor>
    <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/22132/2/Waeckerle-Men_221328.pdf"/>
    <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/22132/2/Waeckerle-Men_221328.pdf"/>
    <dc:creator>Merkle, Hans P.</dc:creator>
    <dc:creator>Scandella, Elke</dc:creator>
    <dc:creator>Waeckerle-Men, Ying</dc:creator>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/22132"/>
    <dc:rights>terms-of-use</dc:rights>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Ludewig, Burkhard</dc:creator>
    <dcterms:title>Phenotype and functional analysis of human monocyte-derived dendritic cells loaded with biodegradable poly(lactide-co-glycolide) microspheres for immunotherapy</dcterms:title>
    <dc:contributor>Waeckerle-Men, Ying</dc:contributor>
    <dc:creator>Uetz-von Allmen, Edith</dc:creator>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:contributor>Ludewig, Burkhard</dc:contributor>
    <dcterms:issued>2004-04</dcterms:issued>
    <dc:creator>Gillessen, Silke</dc:creator>
    <dcterms:abstract xml:lang="deu">Dendritic cells (DC) are increasingly explored as cellular vaccines for tumor immunotherapy. In most reported DC-based cancer vaccine trials, DC have been pulsed with soluble tumor antigen-derived peptide ligands of MHC molecules. Considering that the half-life of peptide/MHC complexes on the cell surface is relatively short and that soluble exogenous protein antigens cannot be efficiently processed via the MHC class I-processing pathway, the current vaccination procedure is not optimal for the induction of strong T cell responses aiming at tumor rejection. Recently, we have shown that antigen presentation can be prolonged when synthetic peptides were encapsulated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres (MS) for uptake by DC. In the present study, we investigated the phenotypic and functional consequences of MS uptake by human monocyte-derived dendritic cells (MoDC) in vitro. We found that immature MoDC that were prepared in serum free media suitable for clinical application were able to phagocytose high numbers of MS, while matured MoDC showed a reduced capacity for phagocytosis of MS. The ingestion of MS did not change the cell surface expression of CD80, CD83, CD86 and HLA-DR of immature and mature DC, suggesting that MS uptake did not induce DC maturation but that maturation by cytokines or LPS was unaltered in the presence of MS. Furthermore, MS-loaded mature MoDC expressed normal levels of the chemokine receptor CCR7 and migrated as efficiently towards CCL19 or CCL21 as unloaded MoDC. DC viability and the secretion of TNF-a and IL-12 was not significantly changed by MS loading. Taken together, our data indicate that PLGA-MS loading has no negative effects on the pivotal properties of MoDC in vitro. It should therefore be feasible to further develop this antigen loading strategy for clinical use in immunotherapy against viral infections and tumors.</dcterms:abstract>
    <dc:creator>Gröttrup, Marcus</dc:creator>
    <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/>
    <dc:contributor>Uetz-von Allmen, Edith</dc:contributor>
    <dcterms:bibliographicCitation>Journal of Immunological Methods ; 287 (2004), 1-2. - S. 109-124</dcterms:bibliographicCitation>
    <dc:creator>Gander, Bruno</dc:creator>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2013-02-26T08:34:59Z</dc:date>
    <dc:language>deu</dc:language>
    <dc:contributor>Gillessen, Silke</dc:contributor>
    <dc:contributor>Gander, Bruno</dc:contributor>
    <dc:contributor>Gröttrup, Marcus</dc:contributor>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Diese Publikation teilen