Recombinant adenylate cyclase toxin of Bordetella pertussis induces cytotoxic T lymphocyte responses against HLA*0201-restricted melanoma epitopes

Détails

ID Serval
serval:BIB_F3CC4CF0B6CD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Recombinant adenylate cyclase toxin of Bordetella pertussis induces cytotoxic T lymphocyte responses against HLA*0201-restricted melanoma epitopes
Périodique
International Immunology
Auteur(s)
Dadaglio  G., Morel  S., Bauche  C., Moukrim  Z., Lemonnier  F. A., Van Den Eynde  B. J., Ladant  D., Leclerc  C.
ISSN
0953-8178 (Print)
Statut éditorial
Publié
Date de publication
12/2003
Volume
15
Numéro
12
Pages
1423-30
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec
Résumé
The adenylate cyclase (CyaA) of Bordetella pertussis is able to deliver CD8(+) T cell epitopes into the cytosol of CD11b(+) dendritic cells (DC) following its specific interaction with the alpha(M)beta(2) integrin (CD11b/CD18). This delivery results in intracellular processing and presentation by MHC class I molecules of the CD8(+) T cell epitopes inserted into CyaA. Indeed, we previously showed that CyaA toxins carrying a single cytotoxic T lymphocyte (CTL) epitope can induce efficient protective and therapeutic antitumor immunity in mice. With a view to elaborating cancer immunotherapy in humans using CyaA, we constructed two recombinant CyaA carrying HLA*0201-restricted melanoma epitopes. Here we show that these recombinant CyaA induce strong anti-melanoma CTL responses in HLA*0201 transgenic mice, even after a single i.v. immunization without adjuvant. These responses are long lasting, since they were also detected 5 months after the last injection. Finally, human DC treated with the recombinant CyaA were shown to process and present efficiently the melanoma epitopes to human CTL clones. Altogether, our results demonstrate that tumoral epitopes inserted into CyaA are efficiently processed and presented in association with human MHC molecules. These observations suggest that CyaA is capable of activating antitumoral CTL in humans and highlight the potential of CyaA for use in cancer immunotherapy.
Mots-clé
Adenylate Cyclase Toxin/genetics/*immunology Aluminum Hydroxide/immunology Animals Catalytic Domain/immunology Cytotoxicity, Immunologic/immunology Dendritic Cells/immunology/metabolism Dose-Response Relationship, Immunologic Epitopes, T-Lymphocyte/*immunology H-2 Antigens/genetics/immunology HLA-A Antigens/genetics/*immunology Humans Immunization Injections, Intraperitoneal Injections, Intravenous Interferon Type II/metabolism Melanoma/*immunology Mice Mice, Knockout Mice, Transgenic Monophenol Monooxygenase/genetics/immunology N-Acetylglucosaminyltransferases/genetics/immunology Peptides/immunology Recombinant Fusion Proteins/genetics/immunology Spleen/cytology T-Lymphocytes, Cytotoxic/*immunology/metabolism beta 2-Microglobulin/genetics/immunology
Pubmed
Web of science
Création de la notice
28/01/2008 10:36
Dernière modification de la notice
03/03/2018 22:43
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