Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC
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 patie...
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Taylor & Francis Group
2016-04-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2015.1071008 |
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| author | 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 Soria Katrin S. Reiners Elke Pogge von Strandmann Frédéric Vély Sylvie Rusakiewicz Alexander Eggermont Jonathan M. Pitt Laurence Zitvogel Nathalie Chaput |
| author_facet | 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 Soria Katrin S. Reiners Elke Pogge von Strandmann Frédéric Vély Sylvie Rusakiewicz Alexander Eggermont Jonathan M. Pitt Laurence Zitvogel Nathalie Chaput |
| author_sort | Benjamin Besse |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c7a0a68f62ab4eb68ba7db4a61d68e2f |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2016-04-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-c7a0a68f62ab4eb68ba7db4a61d68e2f2024-11-15T15:56:38ZengTaylor & Francis GroupOncoImmunology2162-402X2016-04-015410.1080/2162402X.2015.1071008Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLCBenjamin Besse0Mélinda Charrier1Valérie Lapierre2Eric Dansin3Olivier Lantz4David Planchard5Thierry Le Chevalier6Alain Livartoski7Fabrice Barlesi8Agnès Laplanche9Stéphanie Ploix10Nadège Vimond11Isabelle Peguillet12Clotilde Théry13Ludovic Lacroix14Inka Zoernig15Kavita Dhodapkar16Madhav Dhodapkar17Sophie Viaud18Jean-Charles Soria19Katrin S. Reiners20Elke Pogge von Strandmann21Frédéric Vély22Sylvie Rusakiewicz23Alexander Eggermont24Jonathan M. Pitt25Laurence Zitvogel26Nathalie Chaput27Gustave Roussy Cancer Campus, Villejuif, FranceGustave Roussy Cancer Campus, Villejuif, FranceGustave Roussy Cancer Campus, Villejuif, FranceDépartement d'oncologie générale, CLCC Oscar Lambret, Lille, FranceCentre d'Investigation Clinique en Biothérapies (CICBT) 1428, Villejuif, FranceDépartement de Médecine Oncologique (Unité thorax), Gustave Roussy Cancer Campus, Villejuif, FranceDépartement de Médecine Oncologique (Unité thorax), Gustave Roussy Cancer Campus, Villejuif, FranceInstitut Curie, Département de médecine oncologique, Paris, FranceService d'Oncologie Multidisciplinaire & Innovations Thérapeutiques, Université Aix Marseille, Assistance Publique Hôpitaux de Marseille, Marseille, FranceDépartement de Biostatistique et d’épidémiologie, Gustave Roussy Cancer Campus, Villejuif, FranceCentre d'Investigation Clinique en Biothérapies (CICBT) 1428, Villejuif, FranceLaboratoire d'Immunomonitoring en Oncologie, UMS 3655 CNRS / US 23 INSERM Gustave Roussy Cancer Campus, Villejuif, FranceCentre d'Investigation Clinique en Biothérapies (CICBT) 1428, Villejuif, FranceCentre d'Investigation Clinique en Biothérapies (CICBT) 1428, Villejuif, FranceDépartement de biologie et pathologie médicale, Gustave Roussy Cancer Campus, Villejuif, FranceDepartment of Medical Oncology, National Center for Tumor Diseases (NCT) and Heidelberg University Hospital, Heidelberg, GermanyDepartment of Pediatrics, Yale School of Medicine, Yale University, New Haven, CT, USAYale Cancer Center, Yale School of Medicine, Yale University, New Haven, CT, USAGustave Roussy Cancer Campus, Villejuif, FranceGustave Roussy Cancer Campus, Villejuif, FranceDepartment of Internal Medicine I, University Hospital of Cologne, Cologne, GermanyDepartment of Internal Medicine I, University Hospital of Cologne, Cologne, GermanyCentre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, Case 906, FranceGustave Roussy Cancer Campus, Villejuif, FranceGustave Roussy Cancer Campus, Villejuif, FranceGustave Roussy Cancer Campus, Villejuif, FranceGustave Roussy Cancer Campus, Villejuif, FranceGustave Roussy Cancer Campus, Villejuif, FranceDendritic 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.https://www.tandfonline.com/doi/10.1080/2162402X.2015.1071008cancer vaccineexosomesimmunotherapyNSCLCNK cellphase II trial |
| spellingShingle | 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 Soria Katrin S. Reiners Elke Pogge von Strandmann Frédéric Vély Sylvie Rusakiewicz Alexander Eggermont Jonathan M. Pitt Laurence Zitvogel Nathalie Chaput Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC OncoImmunology cancer vaccine exosomes immunotherapy NSCLC NK cell phase II trial |
| title | Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC |
| title_full | Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC |
| title_fullStr | Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC |
| title_full_unstemmed | Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC |
| title_short | Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC |
| title_sort | dendritic cell derived exosomes as maintenance immunotherapy after first line chemotherapy in nsclc |
| topic | cancer vaccine exosomes immunotherapy NSCLC NK cell phase II trial |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2015.1071008 |
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