Memory and effector CD8 T-cell responses after nanoparticle vaccination of melanoma patients.

Détails

ID Serval
serval:BIB_0C5753E658BF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Memory and effector CD8 T-cell responses after nanoparticle vaccination of melanoma patients.
Périodique
Journal of Immunotherapy
Auteur⸱e⸱s
Speiser D.E., Schwarz K., Baumgaertner P., Manolova V., Devevre E., Sterry W., Walden P., Zippelius A., Conzett K.B., Senti G., Voelter V., Cerottini J.P., Guggisberg D., Willers J., Geldhof C., Romero P., Kündig T., Knuth A., Dummer R., Trefzer U., Bachmann M.F.
ISSN
1524-9557
Statut éditorial
Publié
Date de publication
2010
Volume
33
Numéro
8
Pages
848-858
Langue
anglais
Résumé
Induction of cytotoxic CD8 T-cell responses is enhanced by the exclusive presentation of antigen through dendritic cells, and by innate stimuli, such as toll-like receptor ligands. On the basis of these 2 principles, we designed a vaccine against melanoma. Specifically, we linked the melanoma-specific Melan-A/Mart-1 peptide to virus-like nanoparticles loaded with A-type CpG, a ligand for toll-like receptor 9. Melan-A/Mart-1 peptide was cross-presented, as shown in vitro with human dendritic cells and in HLA-A2 transgenic mice. A phase I/II study in stage II-IV melanoma patients showed that the vaccine was well tolerated, and that 14/22 patients generated ex vivo detectable T-cell responses, with in part multifunctional T cells capable to degranulate and produce IFN-γ, TNF-α, and IL-2. No significant influence of the route of immunization (subcutaneous versus intradermal) nor dosing regimen (weekly versus daily clusters) could be observed. It is interesting to note that, relatively large fractions of responding specific T cells exhibited a central memory phenotype, more than what is achieved by other nonlive vaccines. We conclude that vaccination with CpG loaded virus-like nanoparticles is associated with a human CD8 T-cell response with properties of a potential long-term immune protection from the disease.
Mots-clé
melan-A/Mart-1, CD8 T cells, vaccination, virus-like nanoparticles, protective immunity, metastatic melanoma, innate immunity, antigen, lymphocytes, induction, peptides, identification, populations, frequency
Pubmed
Web of science
Création de la notice
24/11/2010 12:25
Dernière modification de la notice
20/08/2019 13:33
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