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Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants

Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants

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ÖHLSCHLÄGER, Peter, Michael QUETTING, Gerardo ALVAREZ, Matthias DÜRST, Lutz GISSMANN, Andreas M. KAUFMANN, 2009. Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants. In: International Journal of Cancer. 125(1), pp. 189-198. ISSN 0020-7136. eISSN 1097-0215. Available under: doi: 10.1002/ijc.24333

@article{Ohlschlager2009Enhan-1263, title={Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants}, year={2009}, doi={10.1002/ijc.24333}, number={1}, volume={125}, issn={0020-7136}, journal={International Journal of Cancer}, pages={189--198}, author={Öhlschläger, Peter and Quetting, Michael and Alvarez, Gerardo and Dürst, Matthias and Gissmann, Lutz and Kaufmann, Andreas M.} }

<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/rdf/resource/123456789/1263"> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/52"/> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/1263"/> <dcterms:bibliographicCitation>Publ. in: International Journal of Cancer 125 (2009), 1, pp. 189-198</dcterms:bibliographicCitation> <dc:creator>Gissmann, Lutz</dc:creator> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:creator>Kaufmann, Andreas M.</dc:creator> <dc:creator>Öhlschläger, Peter</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-23T09:07:30Z</dcterms:available> <dc:contributor>Gissmann, Lutz</dc:contributor> <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/52"/> <dc:contributor>Alvarez, Gerardo</dc:contributor> <dcterms:title>Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants</dcterms:title> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Quetting, Michael</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-23T09:07:30Z</dc:date> <dcterms:issued>2009</dcterms:issued> <dc:creator>Alvarez, Gerardo</dc:creator> <dc:contributor>Öhlschläger, Peter</dc:contributor> <dc:rights>terms-of-use</dc:rights> <dc:creator>Dürst, Matthias</dc:creator> <dcterms:abstract xml:lang="eng">Treatment of patients with cervical cancer by conventional methods (mainly surgery, but also radiotherapy and chemotherapy) results in a significant loss in quality of life. A therapeutic DNA vaccine directed to tumor-specific antigens of the human papilloma virus (HPV) could be an attractive treatment option. We have developed a nontransforming HPV-16 E7-based DNA vaccine containing all putative T cell epitopes (HPV-16 E7SH). DNA vaccines, however, are less immunogenic than protein- or peptide-based vaccines in larger animals and humans. In this study, we have investigated an adjuvant gene support of the HPV-16 E7SH therapeutic cervical cancer vaccine. DNA encoded cytokines (IL-2, IL-12, GM-CSF, IFN-gamma) and the chemokine MIP1-alpha were co-applied either simultaneously or at different time points pre- or post-E7SH vaccination. In addition, sequence-optimized adjuvant genes were compared to wild type genes. Three combinations investigated lead to an enhanced IFN-gamma response of the induced T cells in mice. Interestingly, IFN-gamma secretion of splenocytes did not strictly correlate with tumor response in tumor regression experiments. Gene-encoded MIP-1alpha applied 5 days prior to E7SH-immunization combined with IFN-gamma or IL-12 (3 days) or IL-2 (5 days) postimmunization lead to a significantly enhanced tumor response that was clearly associated with granzyme B secretion and target cells lysis. Our results suggest that a conditioning application and combination with adjuvant genes may be a promising strategy to enhance synergistically immune responses by DNA immunization for the treatment of cervical cancer.</dcterms:abstract> <dc:contributor>Kaufmann, Andreas M.</dc:contributor> <dc:language>eng</dc:language> <dc:contributor>Dürst, Matthias</dc:contributor> <dc:creator>Quetting, Michael</dc:creator> </rdf:Description> </rdf:RDF>

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