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 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.
Tuettenberg
A
A
Department of Dermatology, J. Gutenberg-University, Langenbeckstrasse 1, D-55101 Mainz, Germany.
Jonuleit
H
H
Tüting
T
T
Brück
J
J
Knop
J
J
Enk
A H
AH
D000256:Adenoviridae / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000235:genetics*; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000235:genetics*; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D014161:Transduction, Genetic / Q000379:methods; D058951:gp100 Melanoma Antigen
D019496:Cancer Vaccines; D000939:Epitopes; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D007371:Interferon-gamma