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
Hauptverfasser: TUETTENBERG, A, JONULEIT, H, TÜTING, T, BRÜCK, J, KNOP, J, ENK, A. H
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container_issue 3
container_start_page 243
container_title Gene therapy
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creator TUETTENBERG, A
JONULEIT, H
TÜTING, T
BRÜCK, J
KNOP, J
ENK, A. H
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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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
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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