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Journal Articles OncoImmunology Year : 2016

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

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Benjamin Besse
  • Function : Author
Melinda Charrier
  • Function : Author
Valerie Lapierre
  • Function : Author
Eric Dansin
  • Function : Author
Olivier Lantz
David Planchard
  • Function : Author
Thierry Le Chevalier
  • Function : Author
Alain Livartoski
  • Function : Author
Fabrice Barlesik
  • Function : Author
Agnes Laplanche
  • Function : Author
Stephanie Ploix
  • Function : Author
Nadege Vimond
  • Function : Author
Isabelle Peguillet
  • Function : Author
Clotilde Thery
Ludovic Lacroix
  • Function : Author
Inka Zoernig
  • Function : Author
Kavita Dhodapkar
  • Function : Author
Madhav Dhodapkar
  • Function : Author
Sophie Viaud
  • Function : Author
Jean-Charles Soria
  • Function : Author
Katrin S. Reiners
  • Function : Author
Elke Pogge Von Strandmann
  • Function : Author
Sylvie Rusakiewicz
  • Function : Author
Alexander Eggermont
  • Function : Author
Jonathan M. Pitt
  • Function : Author
Laurence Zitvogel
Nathalie Chaput

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―free) in end-stage cancer, we reported that Dex exerted natural killer (NK) cell effector functions in patients. A second generation of Dex (IFN―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―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―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―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.

Dates and versions

hal-01440237 , version 1 (19-01-2017)

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Benjamin Besse, Melinda Charrier, Valerie Lapierre, Eric Dansin, Olivier Lantz, et al.. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. OncoImmunology, 2016, 5 (4), ⟨10.1080/2162402X.2015.1071008⟩. ⟨hal-01440237⟩

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