Ex vivo detectable activation of Melan-A-specific T cells correlating with inflammatory skin reactions in melanoma patients vaccinated with peptides in IFA.

Détails

ID Serval
serval:BIB_247C151A7AD3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Ex vivo detectable activation of Melan-A-specific T cells correlating with inflammatory skin reactions in melanoma patients vaccinated with peptides in IFA.
Périodique
Cancer Immunity
Auteur(s)
Liénard D., Rimoldi D., Marchand M., Dietrich P.Y., van Baren N., Geldhof C., Batard P., Guillaume P., Ayyoub M., Pittet M.J., Zippelius A., Fleischhauer K., Lejeune F., Cerottini J.C., Romero P., Speiser D.E.
ISSN
1424-9634 (Electronic)
ISSN-L
1424-9634
Statut éditorial
Publié
Date de publication
2004
Volume
4
Pages
4
Langue
anglais
Notes
Publication types: Clinical Trial ; Clinical Trial, Phase I ; Clinical Trial, Phase II ; Controlled Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
The purpose of this study was to test melanoma vaccines consisting of peptides and immunological adjuvants for optimal immunogenicity and to evaluate laboratory immune monitoring for in vivo relevance. Forty-nine HLA-A2 positive patients with Melan-A positive melanoma were repeatedly vaccinated with Melan-A peptide, with or without immune adjuvant AS02B (QS21 and MPL) or IFA. Peptide-specific CD8 T cells in PBLs were analyzed ex vivo using fluorescent HLA-A2/Melan-A multimers and IFN-gamma ELISPOT assays. The vaccines were well tolerated. In vivo expansion of Melan-A-specific CD8 T cells was observed in 13 patients (1/12 after vaccination with peptide in AS02B and 12/17 after vaccination with peptide in IFA). The T cells produced IFN-gamma and downregulated CD45RA and CD28. T-cell responses correlated with inflammatory skin reactions at vaccine injection sites (P < 0.001) and with DTH reaction to Melan-A peptide (P < 0.01). Twenty-six of 32 evaluable patients showed progressive disease, whereas 4 patients had stable disease. The two patients with the strongest Melan-A-specific T-cell responses experienced regression of metastases in skin, lymph nodes, and lung. We conclude that repeated vaccination with Melan-A peptide in IFA frequently leads to sustained responses of specific CD8 T cells that are detectable ex vivo and correlate with inflammatory skin reactions.
Mots-clé
Adolescent, Adult, Aged, Antigens, Neoplasm, CD8-Positive T-Lymphocytes/immunology, Cancer Vaccines/immunology, Cancer Vaccines/toxicity, Dermatitis/etiology, Disease Progression, Female, Freund's Adjuvant/therapeutic use, Humans, Lipids/therapeutic use, Lymphocyte Activation, MART-1 Antigen, Male, Melanoma/diagnosis, Melanoma/immunology, Middle Aged, Monitoring, Immunologic, Neoplasm Proteins/immunology, Peptides/immunology, Peptides/therapeutic use, Viral Matrix Proteins/immunology
Pubmed
Création de la notice
28/01/2008 12:14
Dernière modification de la notice
20/08/2019 14:02
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