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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.

Authors :
Legat A
Maby-El Hajjami H
Baumgaertner P
Cagnon L
Abed Maillard S
Geldhof C
Iancu EM
Lebon L
Guillaume P
Dojcinovic D
Michielin O
Romano E
Berthod G
Rimoldi D
Triebel F
Luescher I
Rufer N
Speiser DE
Source :
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2016 Mar 15; Vol. 22 (6), pp. 1330-40. Date of Electronic Publication: 2015 Oct 23.
Publication Year :
2016

Abstract

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.<br />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.<br />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.<br />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.<br /> (©2015 American Association for Cancer Research.)

Details

Language :
English
ISSN :
1557-3265
Volume :
22
Issue :
6
Database :
MEDLINE
Journal :
Clinical cancer research : an official journal of the American Association for Cancer Research
Publication Type :
Academic Journal
Accession number :
26500235
Full Text :
https://doi.org/10.1158/1078-0432.CCR-15-1212