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Updated technology to produce highly immunogenic dendritic cell-derived exosomes of clinical grade: a critical role of interferon-γ.

Authors
  • Viaud, Sophie
  • Ploix, Stéphanie
  • Lapierre, Valérie
  • Théry, Clotilde
  • Commere, Pierre-Henri
  • Tramalloni, Dominique
  • Gorrichon, Kevin
  • Virault-Rocroy, Pauline
  • Tursz, Thomas
  • Lantz, Olivier
  • Zitvogel, Laurence
  • Chaput, Nathalie
Type
Published Article
Journal
Journal of Immunotherapy
Publisher
Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins
Publication Date
Jan 01, 2011
Volume
34
Issue
1
Pages
65–75
Identifiers
DOI: 10.1097/CJI.0b013e3181fe535b
PMID: 21150714
Source
Medline
License
Unknown

Abstract

Dendritic cell-derived exosomes (Dex) are nanovesicles bearing major histocompatibility complexes promoting T-cell-dependent antitumor effects in mice. Two phase I clinical trials aimed at vaccinating cancer patients with peptide-pulsed Dex have shown the feasibility and safety of inoculating clinical-grade Dex, but have failed to show their immunizing capacity. These low immunogenic capacities have led us to develop second-generation Dex with enhanced immunostimulatory properties. Here, we show that interferon-γ is a key cytokine conditioning the dendritic cell to induce the expression of CD40, CD80, CD86, and CD54 on Dex, endowing them with direct and potent peptide-dependent CD8(+) T-cell-triggering potential in vitro and in vivo. In this study, we describe the clinical grade process to manufacture large-scale interferon-γ-Dex vaccines and their quality control parameters currently used in a phase II trial.

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