title: Updated technology to produce highly immunogenic dendritic cell-derived exosomes of clinical grade: a critical role of interferon-γ.
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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U1015, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Viaud
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ploix
authors.forename: Valérie
authors.initials: V
authors.lastname: Lapierre
authors.forename: Clotilde
authors.initials: C
authors.lastname: Théry
authors.forename: Pierre-Henri
authors.initials: PH
authors.lastname: Commere
authors.forename: Dominique
authors.initials: D
authors.lastname: Tramalloni
authors.forename: Kevin
authors.initials: K
authors.lastname: Gorrichon
authors.forename: Pauline
authors.initials: P
authors.lastname: Virault-Rocroy
authors.forename: Thomas
authors.initials: T
authors.lastname: Tursz
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chaput
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics; D051940:B7-2 Antigen / Q000235:genetics; D019013:CD40 Antigens; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D055354:Exosomes / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007371:Interferon-gamma / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D019496:Cancer Vaccines; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma