Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC

• Published in: Oncoimmunology 2016-04, Vol.5 (4), p.e1071008
• Main Authors: Besse, Benjamin, Charrier, Mélinda, Lapierre, Valérie, Dansin, Eric, Lantz, Olivier, Planchard, David, Le Chevalier, Thierry, Livartoski, Alain, Barlesi, Fabrice, Laplanche, Agnès, Ploix, Stéphanie, Vimond, Nadège, Peguillet, Isabelle, Théry, Clotilde, Lacroix, Ludovic, Zoernig, Inka, Dhodapkar, Kavita, Dhodapkar, Madhav, Viaud, Sophie, Soria, Jean-Charles, Reiners, Katrin S., Pogge von Strandmann, Elke, Vély, Frédéric, Rusakiewicz, Sylvie, Eggermont, Alexander, Pitt, Jonathan M., Zitvogel, Laurence, Chaput, Nathalie
• Format: Article
• Language: English
• Subjects: cancer vaccine; exosomes; Immunology; immunotherapy; Life Sciences; NK cell; NSCLC; Original Research; phase II trial
• ISSN: 2162-4011; 2162-402X; 2162-402X
• DOI: 10.1080/2162402X.2015.1071008

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.