Priming of T cells with Ad-transduced DC followed by expansion with peptide-pulsed DC significantly enhances the induction of tumor-specific CD8 T cells: implications for an efficient vaccination strategy
In recent years, vaccination strategies using antigen-presenting cells (APC) have been under investigation. Antigen delivery using genetic immunization through ex vivo transduction of dendritic cells (DC) is supposed to enhance the induction of antitumor responses in humans by activating a broad ran...
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Veröffentlicht in: | Gene therapy 2003-02, Vol.10 (3), p.243-250 |
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description | In recent years, vaccination strategies using antigen-presenting cells (APC) have been under investigation. Antigen delivery using genetic immunization through ex vivo transduction of dendritic cells (DC) is supposed to enhance the induction of antitumor responses in humans by activating a broad range of peptide-specific CD8+ T cells. In this study, we compared the potential of adenoviral (Ad)-transduced versus peptide-pulsed DC to induce melanoma-antigen (Ag)-specific T-cell responses in vitro. Whereas gp100-peptide-pulsed DC induced long-lasting specific CD8+ T-cell responses against single peptides, Ad-transduced DC induced broad and strong, specific immunity against various peptides of the gp100-Ag. Surprisingly, several restimulations led to decreasing gp100-specific and in parallel to increasing anti-adenoviral T-cell responses. Nevertheless, those anti-adenoviral T-cell responses provided an "adjuvant" effect by inducing an early release of high amounts of IL-2/IFN-gamma, therewith enhancing CTL induction in the initiation phase. Based on these data, we suggest a prime/boost vaccination strategy in melanoma patients--combining the use of Ad-DC and peptide-pulsed DC--to obtain efficient and long-term antitumor T-cell responses. |
doi_str_mv | 10.1038/sj.gt.3301880 |
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Nevertheless, those anti-adenoviral T-cell responses provided an "adjuvant" effect by inducing an early release of high amounts of IL-2/IFN-gamma, therewith enhancing CTL induction in the initiation phase. Based on these data, we suggest a prime/boost vaccination strategy in melanoma patients--combining the use of Ad-DC and peptide-pulsed DC--to obtain efficient and long-term antitumor T-cell responses.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/sj.gt.3301880</identifier><identifier>PMID: 12571632</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>Adenoviridae - genetics ; Biological and medical sciences ; Cancer Vaccines ; CD8-Positive T-Lymphocytes - immunology ; Cell Line ; Dendritic Cells - immunology ; Epitopes - genetics ; Fundamental and applied biological sciences. Psychology ; Genetic Therapy - methods ; Genetic Vectors - administration & dosage ; gp100 Melanoma Antigen ; Humans ; Interferon-gamma - immunology ; Interleukin-2 - immunology ; Melanoma - immunology ; Melanoma - therapy ; Membrane Glycoproteins - administration & dosage ; Membrane Glycoproteins - genetics ; Molecular and cellular biology ; Neoplasm Proteins - administration & dosage ; Neoplasm Proteins - genetics ; Skin Neoplasms - immunology ; Skin Neoplasms - therapy ; Transduction, Genetic - methods</subject><ispartof>Gene therapy, 2003-02, Vol.10 (3), p.243-250</ispartof><rights>2003 INIST-CNRS</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Feb 1, 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27933,27934</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14686972$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12571632$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>TUETTENBERG, A</creatorcontrib><creatorcontrib>JONULEIT, H</creatorcontrib><creatorcontrib>TÜTING, T</creatorcontrib><creatorcontrib>BRÜCK, J</creatorcontrib><creatorcontrib>KNOP, J</creatorcontrib><creatorcontrib>ENK, A. H</creatorcontrib><title>Priming of T cells with Ad-transduced DC followed by expansion with peptide-pulsed DC significantly enhances the induction of tumor-specific CD8 T cells: implications for an efficient vaccination strategy</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><description>In recent years, vaccination strategies using antigen-presenting cells (APC) have been under investigation. Antigen delivery using genetic immunization through ex vivo transduction of dendritic cells (DC) is supposed to enhance the induction of antitumor responses in humans by activating a broad range of peptide-specific CD8+ T cells. In this study, we compared the potential of adenoviral (Ad)-transduced versus peptide-pulsed DC to induce melanoma-antigen (Ag)-specific T-cell responses in vitro. Whereas gp100-peptide-pulsed DC induced long-lasting specific CD8+ T-cell responses against single peptides, Ad-transduced DC induced broad and strong, specific immunity against various peptides of the gp100-Ag. Surprisingly, several restimulations led to decreasing gp100-specific and in parallel to increasing anti-adenoviral T-cell responses. Nevertheless, those anti-adenoviral T-cell responses provided an "adjuvant" effect by inducing an early release of high amounts of IL-2/IFN-gamma, therewith enhancing CTL induction in the initiation phase. 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H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Priming of T cells with Ad-transduced DC followed by expansion with peptide-pulsed DC significantly enhances the induction of tumor-specific CD8 T cells: implications for an efficient vaccination strategy</atitle><jtitle>Gene therapy</jtitle><addtitle>Gene Ther</addtitle><date>2003-02-01</date><risdate>2003</risdate><volume>10</volume><issue>3</issue><spage>243</spage><epage>250</epage><pages>243-250</pages><issn>0969-7128</issn><eissn>1476-5462</eissn><abstract>In recent years, vaccination strategies using antigen-presenting cells (APC) have been under investigation. Antigen delivery using genetic immunization through ex vivo transduction of dendritic cells (DC) is supposed to enhance the induction of antitumor responses in humans by activating a broad range of peptide-specific CD8+ T cells. In this study, we compared the potential of adenoviral (Ad)-transduced versus peptide-pulsed DC to induce melanoma-antigen (Ag)-specific T-cell responses in vitro. Whereas gp100-peptide-pulsed DC induced long-lasting specific CD8+ T-cell responses against single peptides, Ad-transduced DC induced broad and strong, specific immunity against various peptides of the gp100-Ag. Surprisingly, several restimulations led to decreasing gp100-specific and in parallel to increasing anti-adenoviral T-cell responses. Nevertheless, those anti-adenoviral T-cell responses provided an "adjuvant" effect by inducing an early release of high amounts of IL-2/IFN-gamma, therewith enhancing CTL induction in the initiation phase. Based on these data, we suggest a prime/boost vaccination strategy in melanoma patients--combining the use of Ad-DC and peptide-pulsed DC--to obtain efficient and long-term antitumor T-cell responses.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>12571632</pmid><doi>10.1038/sj.gt.3301880</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adenoviridae - genetics Biological and medical sciences Cancer Vaccines CD8-Positive T-Lymphocytes - immunology Cell Line Dendritic Cells - immunology Epitopes - genetics Fundamental and applied biological sciences. Psychology Genetic Therapy - methods Genetic Vectors - administration & dosage gp100 Melanoma Antigen Humans Interferon-gamma - immunology Interleukin-2 - immunology Melanoma - immunology Melanoma - therapy Membrane Glycoproteins - administration & dosage Membrane Glycoproteins - genetics Molecular and cellular biology Neoplasm Proteins - administration & dosage Neoplasm Proteins - genetics Skin Neoplasms - immunology Skin Neoplasms - therapy Transduction, Genetic - methods |
title | Priming of T cells with Ad-transduced DC followed by expansion with peptide-pulsed DC significantly enhances the induction of tumor-specific CD8 T cells: implications for an efficient vaccination strategy |
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