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

Benjamin Besse, Mélinda Charrier, Valérie Lapierre, Eric Dansin, Olivier Lantz, David Planchard, Thierry Le Chevalier, Alain Livartoski, Fabrice Barlesi, Agnès Laplanche, Stéphanie Ploix, Nadège Vimond, Isabelle Peguillet, Clotilde Théry, Ludovic Lacroix, Inka Zoernig, Kavita Dhodapkar, Madhav Dhodapkar, Sophie Viaud, Jean Charles SoriaKatrin S. Reiners, Elke Pogge von Strandmann, Frédéric Vély, Sylvie Rusakiewicz, Alexander Eggermont, Jonathan M. Pitt, Laurence Zitvogel, Nathalie Chaput

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

534 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
TijdschriftOncoImmunology
Volume5
Nummer van het tijdschrift4
DOI's
StatusGepubliceerd - 2 apr. 2016
Extern gepubliceerdJa

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