title: Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC.
abstract: Dendritic cell-derived exosomes (Dex) are small extracellular vesicles secreted by viable dendritic cells. In the two phase-I trials that we conducted using the first generation of Dex (IFN-γ-free) in end-stage cancer, we reported that Dex exerted natural killer (NK) cell effector functions in patients. A second generation of Dex (IFN-γ-Dex) was manufactured with the aim of boosting NK and T cell immune responses. We carried out a phase II clinical trial testing the clinical benefit of IFN-γ-Dex loaded with MHC class I- and class II-restricted cancer antigens as maintenance immunotherapy after induction chemotherapy in patients bearing inoperable non-small cell lung cancer (NSCLC) without tumor progression. The primary endpoint was to observe at least 50% of patients with progression-free survival (PFS) at 4 mo after chemotherapy cessation. Twenty-two patients received IFN-γ-Dex. One patient exhibited a grade three hepatotoxicity. The median time to progression was 2.2 mo and median overall survival (OS) was 15 mo. Seven patients (32%) experienced stabilization of >4 mo. The primary endpoint was not reached. An increase in NKp30-dependent NK cell functions were evidenced in a fraction of these NSCLC patients presenting with defective NKp30 expression. Importantly, MHC class II expression levels of the final IFN-γ-Dex product correlated with expression levels of the NKp30 ligand BAG6 on Dex, and with NKp30-dependent NK functions, the latter being associated with longer progression-free survival. This phase II trial confirmed the capacity of Dex to boost the NK cell arm of antitumor immunity in patients with advanced NSCLC.
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; Département de Médecine Oncologique (Unité thorax), Gustave Roussy Cancer Campus, Villejuif, France; Faculté de médecine, Université Paris Sud, Le Kremlin-Bicêtre, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; Faculté de médecine, Université Paris Sud, Le Kremlin-Bicêtre, France; Laboratoire d'Immunomonitoring en Oncologie, UMS 3655 CNRS / US 23 INSERM Gustave Roussy Cancer Campus, Villejuif, France; Centre d'Investigation Clinique en Biothérapies (CICBT) 1428, Villejuif, France.
authors.forename: Mélinda
authors.initials: M
authors.lastname: Charrier
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; Laboratoire de Thérapie Cellulaire, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Lapierre
authors.affiliation: Département d'oncologie générale, CLCC Oscar Lambret , Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Dansin
authors.affiliation: Centre d'Investigation Clinique en Biothérapies (CICBT) 1428, Villejuif, France; Laboratoire d'Immunologie Clinique, Institut Curie, Paris, France; Inserm U932, Institut Curie, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
authors.affiliation: Département de Médecine Oncologique (Unité thorax), Gustave Roussy Cancer Campus , Villejuif, France.
authors.forename: David
authors.initials: D
authors.lastname: Planchard
authors.affiliation: Département de Médecine Oncologique (Unité thorax), Gustave Roussy Cancer Campus , Villejuif, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Le Chevalier
authors.affiliation: Institut Curie, Département de médecine oncologique , Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Livartoski
authors.affiliation: Service d'Oncologie Multidisciplinaire & Innovations Thérapeutiques, Université Aix Marseille, Assistance Publique Hôpitaux de Marseille , Marseille, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlesi
authors.affiliation: Département de Biostatistique et d'épidémiologie, Gustave Roussy Cancer Campus , Villejuif, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Laplanche
authors.affiliation: Centre d'Investigation Clinique en Biothérapies (CICBT) 1428, Villejuif, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Ploix
authors.affiliation: Laboratoire d'Immunomonitoring en Oncologie, UMS 3655 CNRS / US 23 INSERM Gustave Roussy Cancer Campus, Villejuif, France; Centre d'Investigation Clinique en Biothérapies (CICBT) 1428, Villejuif, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Vimond
authors.affiliation: Centre d'Investigation Clinique en Biothérapies (CICBT) 1428, Villejuif, France; Laboratoire d'Immunologie Clinique, Institut Curie, Paris, France; Inserm U932, Institut Curie, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Peguillet
authors.affiliation: Centre d'Investigation Clinique en Biothérapies (CICBT) 1428, Villejuif, France; Inserm U932, Institut Curie, Paris, France.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Théry
authors.affiliation: Département de biologie et pathologie médicale, Gustave Roussy Cancer Campus, Villejuif, France; Laboratoire de Recherche Translationnelle, UMS 3655 CNRS / US 23 INSERM Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lacroix
authors.affiliation: Department of Medical Oncology, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital , Heidelberg, Germany.
authors.forename: Inka
authors.initials: I
authors.lastname: Zoernig
authors.affiliation: Department of Pediatrics, Yale School of Medicine, Yale University, New Haven, CT, USA; Yale Cancer Center, Yale School of Medicine, Yale University, New Haven, CT, USA.
authors.forename: Kavita
authors.initials: K
authors.lastname: Dhodapkar
authors.affiliation: Yale Cancer Center, Yale School of Medicine, Yale University, New Haven, CT, USA; Department of Medicine, Yale School of Medicine, Yale University, New Haven, CT, USA; Department of Immunobiology, Yale School of Medicine, Yale University, New Haven, CT, USA.
authors.forename: Madhav
authors.initials: M
authors.lastname: Dhodapkar
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; Faculté de médecine, Université Paris Sud, Le Kremlin-Bicêtre, France; INSERM, U1015, Villejuif, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Viaud
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; Faculté de médecine, Université Paris Sud, Le Kremlin-Bicêtre, France; INSERM, U981, Villejuif, France; Département d'Innovation Thérapeutique et d'Essais Précoces, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Department of Internal Medicine I, University Hospital of Cologne , Cologne, Germany.
authors.forename: Katrin S
authors.initials: KS
authors.lastname: Reiners
authors.affiliation: Department of Internal Medicine I, University Hospital of Cologne , Cologne, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Pogge von Strandmann
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Case 906, France; INSERM, U1104, Marseille, France; CNRS, UMR7280, Marseille, France; Laboratoire d'immunologie- Hôpital de la Conception, Assistance Publique - Hôpitaux de Marseille, Marseille, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Vély
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; Centre d'Investigation Clinique en Biothérapies (CICBT) 1428, Villejuif, France; INSERM, U1015, Villejuif, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rusakiewicz
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; Faculté de médecine, Université Paris Sud, Le Kremlin-Bicêtre, France; INSERM, U1015, Villejuif, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Eggermont
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; Faculté de médecine, Université Paris Sud, Le Kremlin-Bicêtre, France; INSERM, U1015, Villejuif, France.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Pitt
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; Faculté de médecine, Université Paris Sud, Le Kremlin-Bicêtre, France; Centre d'Investigation Clinique en Biothérapies (CICBT) 1428, Villejuif, France; INSERM, U1015, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.affiliation: Gustave Roussy Cancer Campus, Villejuif, France; Laboratoire d'Immunomonitoring en Oncologie, UMS 3655 CNRS / US 23 INSERM Gustave Roussy Cancer Campus, Villejuif, France; Centre d'Investigation Clinique en Biothérapies (CICBT) 1428, Villejuif, France; Laboratoire de Thérapie Cellulaire, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chaput
keywords: NK cell; NSCLC; cancer vaccine; exosomes; immunotherapy; phase II trial