Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients.

Détails

Ressource 1Télécharger: BIB_FA34B494C8D3.P001.pdf (1290.04 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_FA34B494C8D3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients.
Périodique
European Journal of Immunology
Auteur(s)
Goldinger S.M., Dummer R., Baumgaertner P., Mihic-Probst D., Schwarz K., Hammann-Haenni A., Willers J., Geldhof C., Prior J.O., Kündig T.M., Michielin O., Bachmann M.F., Speiser D.E.
ISSN
1521-4141 (Electronic)
ISSN-L
0014-2980
Statut éditorial
Publié
Date de publication
2012
Volume
42
Numéro
11
Pages
3049-3061
Langue
anglais
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Optimal vaccine strategies must be identified for improving T-cell vaccination against infectious and malignant diseases. MelQbG10 is a virus-like nano-particle loaded with A-type CpG-oligonucleotides (CpG-ODN) and coupled to peptide(16-35) derived from Melan-A/MART-1. In this phase IIa clinical study, four groups of stage III-IV melanoma patients were vaccinated with MelQbG10, given (i) with IFA (Montanide) s.c.; (ii) with IFA s.c. and topical Imiquimod; (iii) i.d. with topical Imiquimod; or (iv) as intralymph node injection. In total, 16/21 (76%) patients generated ex vivo detectable Melan-A/MART-1-specific T-cell responses. T-cell frequencies were significantly higher when IFA was used as adjuvant, resulting in detectable T-cell responses in all (11/11) patients, with predominant generation of effector-memory-phenotype cells. In turn, Imiquimod induced higher proportions of central-memory-phenotype cells and increased percentages of CD127(+) (IL-7R) T cells. Direct injection of MelQbG10 into lymph nodes resulted in lower T-cell frequencies, associated with lower proportions of memory and effector-phenotype T cells. Swelling of vaccine site draining lymph nodes, and increased glucose uptake at PET/CT was observed in 13/15 (87%) of evaluable patients, reflecting vaccine triggered immune reactions in lymph nodes. We conclude that the simultaneous use of both Imiquimod and CpG-ODN induced combined memory and effector CD8(+) T-cell responses.
Mots-clé
Adjuvants, Immunologic/administration & dosage, Aminoquinolines/administration & dosage, CD8-Positive T-Lymphocytes/immunology, Cancer Vaccines/administration & dosage, Cancer Vaccines/adverse effects, Flow Cytometry, Freund's Adjuvant/administration & dosage, Humans, Immunologic Memory/immunology, Ligands, Lipids/administration & dosage, MART-1 Antigen/immunology, Melanoma/immunology, Melanoma/therapy, Nanoparticles/administration & dosage, Oligodeoxyribonucleotides/immunology, Skin Neoplasms/immunology, Statistics, Nonparametric, Toll-Like Receptor 7/immunology, Toll-Like Receptor 9/immunology
Pubmed
Web of science
Création de la notice
22/10/2012 16:26
Dernière modification de la notice
03/03/2018 22:55
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