Titre
Vaccination with LAG-3Ig (IMP321) and peptides induces specific CD4 and CD8 T-cell responses in metastatic melanoma patients - report of a phase I/IIa clinical trial.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Legat, A.
Auteure/Auteur
Maby-El Hajjami, H.
Auteure/Auteur
Baumgaertner, P.
Auteure/Auteur
Cagnon, L.
Auteure/Auteur
Abed Maillard, S.
Auteure/Auteur
Geldhof, C.
Auteure/Auteur
Iancu, E.M.
Auteure/Auteur
Lebon, L.
Auteure/Auteur
Guillaume, P.
Auteure/Auteur
Dojcinovic, D.
Auteure/Auteur
Michielin, O.
Auteure/Auteur
Romano, E.
Auteure/Auteur
Berthod, G.
Auteure/Auteur
Rimoldi, D.
Auteure/Auteur
Triebel, F.
Auteure/Auteur
Luescher, I.
Auteure/Auteur
Rufer, N.
Auteure/Auteur
Speiser, D.E.
Auteure/Auteur
Liens vers les unités
ISSN
1078-0432
Statut éditorial
Publié
Date de publication
2016
Volume
22
Numéro
6
Première page
1330
Dernière page/numéro d’article
1340
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: journal article.
Publication status: published.
Publication status: published.
Résumé
PURPOSE: Cancer vaccines aim to generate and maintain antitumor immune responses. We designed a phase I/IIa clinical trial to test a vaccine formulation composed of Montanide ISA-51 (Incomplete Freund's Adjuvant), LAG-3Ig (IMP321, a non-Toll like Receptor agonist with adjuvant properties), and five synthetic peptides derived from tumor-associated antigens (four short 9/10-mers targeting CD8 T-cells, and one longer 15-mer targeting CD4 T-cells). Primary endpoints were safety and T-cell responses.
EXPERIMENTAL DESIGN: Sixteen metastatic melanoma patients received serial vaccinations. Up to nine injections were subcutaneously administered in three cycles, each with three vaccinations every 3 weeks, with 6 to 14 weeks interval between cycles. Blood samples were collected at baseline, 1-week after the third, sixth and ninth vaccination, and 6 months after the last vaccination. Circulating T-cells were monitored by tetramer staining directly ex vivo, and by combinatorial tetramer and cytokine staining on in vitro stimulated cells.
RESULTS: Side effects were mild to moderate, comparable to vaccines with Montanide alone. Specific CD8 T-cell responses to at least one peptide formulated in the vaccine preparation were found in 13 of 16 patients. However, two of the four short peptides of the vaccine formulation did not elicit CD8 T-cell responses. Specific CD4 T-cell responses were found in all 16 patients.
CONCLUSIONS: We conclude that vaccination with IMP321 is a promising and safe strategy for inducing sustained immune responses, encouraging further development for cancer vaccines as components of combination therapies. Clin Cancer Res; 22(6); 1330-40. ©2015 AACR.
EXPERIMENTAL DESIGN: Sixteen metastatic melanoma patients received serial vaccinations. Up to nine injections were subcutaneously administered in three cycles, each with three vaccinations every 3 weeks, with 6 to 14 weeks interval between cycles. Blood samples were collected at baseline, 1-week after the third, sixth and ninth vaccination, and 6 months after the last vaccination. Circulating T-cells were monitored by tetramer staining directly ex vivo, and by combinatorial tetramer and cytokine staining on in vitro stimulated cells.
RESULTS: Side effects were mild to moderate, comparable to vaccines with Montanide alone. Specific CD8 T-cell responses to at least one peptide formulated in the vaccine preparation were found in 13 of 16 patients. However, two of the four short peptides of the vaccine formulation did not elicit CD8 T-cell responses. Specific CD4 T-cell responses were found in all 16 patients.
CONCLUSIONS: We conclude that vaccination with IMP321 is a promising and safe strategy for inducing sustained immune responses, encouraging further development for cancer vaccines as components of combination therapies. Clin Cancer Res; 22(6); 1330-40. ©2015 AACR.
PID Serval
serval:BIB_9AB3B918AF4A
PMID
Open Access
Oui
Date de création
2016-05-01T15:41:46.897Z
Date de création dans IRIS
2025-05-20T22:06:56Z
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Nom
26500235AM.pdf
Version du manuscrit
published
Taille
2.81 MB
Format
Adobe PDF
PID Serval
serval:BIB_9AB3B918AF4A.P001
URN
urn:nbn:ch:serval-BIB_9AB3B918AF4A1
Somme de contrôle
(MD5):fedc5b5fcb439b4a73df847a197fa001