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

By B. Besse, M. Charrier, V. Lapierre, É. Dansin, O. Lantz, D. Planchard, T. le Chevalier, Alain Livartoski, F. Barlesi, A. Laplanche and 18 more. Oncoimmunology, 2015

690 citations recorded by the source corpus.

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.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7a2a5df6994f9a3f8dd2c74893dd79eb11a5e686

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Citations in the corpus

Shedding light on the cell biology of extracellular vesicles (2018, positive): “Their use in clinical research have already demonstrated that extracellular vesicles secreted by immune cells (dendritic cells) stimulate the immune system and can therefore be exploited as anti-766 tumor vaccines 176,177 .”
The biology, function, and biomedical applications of exosomes (2020, neutral): “Although the approach did not yield a measurable cancer-specific T cell response, dexosomes induced increased cytolytic activity associated with natural killer cells in patients with stage IIIB/IV non–small-cell lung cancer (234).”
Manufacturing Exosomes: A Promising Therapeutic Platform. (2018, neutral): “These include the use of autologous, modified dendritic-derived EVs for maintenance immunotherapy [32,33], allogeneic MSC-derived EVs for the treatment of chronic kidney disease [34], type 1 diabetes mellitus (clinical trial NCT02138331), acute ischemic stroke (clinical trial NCT03384433), and autol”
Advances in therapeutic applications of extracellular vesicles (2019, background): “Non–small cell lung cancer (95) [NCT01159288] Phase 2, n = 22 mDCs, autologous Pulsed with peptides 32% with stable disease, primary endpoint (>50%) not reached”
Exosome-Based Cell-Cell Communication in the Tumor Microenvironment (2018, background): “In addition, two phase I (Escudier et al., 2005; Morse et al., 2005) and one phase II clinical trial (Besse et al., 2016) using DC-derived exosomes have now been completed, showing the feasibility and safety of this approach.”
Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper (2015, background): “However, in some patients, a positive effect on natural killer (NK) cell activity was observed (22).”
Innovative approaches for cancer treatment: current perspectives and new challenges (2019, background): “Autologous dendritic cell-derived exosomes with improved immunostimulatory function have been tested in a phase II clinical trial for the activation of CD8+ T cells [91] in non-small cell lung cancer (NSCLC) patients, observing disease stabilisation and a better overall survival [92].”