Besse, Benjamin ORCID: 0000-0001-5090-8189, Charrier, Melinda, Lapierre, Valerie, Dansin, Eric, Lantz, Olivier, Planchard, David, Le Chevalier, Thierry, Livartoski, Alain, Barlesik, Fabrice, Laplanche, Agnes, Ploix, Stephanie, Vimond, Nadege, Peguillet, Isabelle, Thery, Clotilde, Lacroix, Ludovic, Zoernig, Inka, Dhodapkar, Kavita, Dhodapkar, Madhav, Viaud, Sophie, Soria, Jean-Charles, Reiners, Katrin S., von Strandmann, Elke Pogge, Vely, Frederic ORCID: 0000-0002-1682-0949, Rusakiewicz, Sylvie, Eggermont, Alexander, Pitt, Jonathan M., Zitvogel, Laurence and Chaput, Nathalie (2016). Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. OncoImmunology, 5 (4). PHILADELPHIA: TAYLOR & FRANCIS INC. ISSN 2162-402X

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Besse, BenjaminUNSPECIFIEDorcid.org/0000-0001-5090-8189UNSPECIFIED
Charrier, MelindaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lapierre, ValerieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dansin, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lantz, OlivierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Planchard, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Le Chevalier, ThierryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Livartoski, AlainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barlesik, FabriceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laplanche, AgnesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ploix, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vimond, NadegeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peguillet, IsabelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thery, ClotildeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lacroix, LudovicUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zoernig, InkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dhodapkar, KavitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dhodapkar, MadhavUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Viaud, SophieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soria, Jean-CharlesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reiners, Katrin S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Strandmann, Elke PoggeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vely, FredericUNSPECIFIEDorcid.org/0000-0002-1682-0949UNSPECIFIED
Rusakiewicz, SylvieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eggermont, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pitt, Jonathan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zitvogel, LaurenceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chaput, NathalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-293212
DOI: 10.1080/2162402X.2015.1071008
Journal or Publication Title: OncoImmunology
Volume: 5
Number: 4
Date: 2016
Publisher: TAYLOR & FRANCIS INC
Place of Publication: PHILADELPHIA
ISSN: 2162-402X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
IMMUNE-SYSTEM; PROGNOSTIC VALUE; CLINICAL GRADE; CHAPERONE; RECEPTOR; HSP70; EXPRESSION; RESPONSES; NKP30Multiple languages
Oncology; ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/29321

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