Dendritic Cell–Derived Exosomes as Immunotherapies in the Fight against Cancer

Pitt, Jonathan M.; Charrier, Mélinda; Viaud, Sophie; André, Fabrice; Besse, Benjamin; Chaput, Nathalie; Zitvogel, Laurence

doi:10.4049/jimmunol.1400703

Cited by 238 publications

(169 citation statements)

References 50 publications

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“…68 As indicated above, DEXs present peptide-loaded MHC Class I and II complexes to stimulate both CD8 C CTL and CD4 C T cell responses, collaborating with co-stimulatory and adhesion molecules. 69 In addition, MHC class I-restricted, peptide-specific CTL priming is critical for effective antitumor responses. 70 Interestingly, CTL responses mediated by DEXs were not only dependent on CD4 C T cells but also on B cells.…”

Section: Exosome-mediated Activation Of Immune Response Against Tumorsmentioning

confidence: 99%

The exosomes in tumor immunity

2015

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Exosomes are a kind of nanometric membrane vesicles and can be released by almost all kinds of cells, including cancer cells. As the important mediators in intercellular communications, exosomes mediate exchange of protein and genetic material derived from parental cells. Emerging evidences show that exosomes secreted by either host cells or cancer cells are involved in tumor initiation, growth, invasion and metastasis. Moreover, communications between immune cells and cancer cells via exosomes play dual roles in modulating tumor immunity. In this review, we focus on exosome-mediated immunosuppression via inhibition of antitumor responses elicited by immune cells (DCs, NK cells, CD4 C and CD8 C T cells, etc.) and induction of immunosuppressive or regulatory cell populations (MDSCs, Tregs and Bregs). Transfer of cytokines, microRNAs (miRNAs) and functional mRNAs by tumor-derived exosomes (TEXs) is crucial in the immune escape. Furthermore, exosomes secreted from several kinds of immune cells (DCs, CD4 C and CD8 C Tregs) also participate in immunosuppression. On the other hand, we summarize the current application of DCderived and modified tumor-derived exosomes as tumor vaccines. The potential challenges about exosome-based vaccines for clinical application are also discussed.

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Section: Exosome-mediated Activation Of Immune Response Against Tumorsmentioning

confidence: 99%

The exosomes in tumor immunity

2015

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“…Implementing such therapies across large populations is costly, requires dedicated expertise, and requires monitoring of well-defined quality control parameters. Furthermore, it is difficult to store DCs over long periods of time while maintaining their efficacy (4).…”

Section: Introductionmentioning

confidence: 99%

Dendritic cell–derived exosomes for cancer therapy

Pitt¹,

André²,

Amigorena³

et al. 2016

Journal of Clinical Investigation

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466

389

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International audienceDC-derived exosomes (Dex) are nanometer-sized membrane vesicles that are secreted by the sentinel antigen-presenting cells of the immune system: DCs. Like DCs, the molecular composition of Dex includes surface expression of functional MHC-peptide complexes, costimulatory molecules, and other components that interact with immune cells. Dex have the potential to facilitate immune cell–dependent tumor rejection and have distinct advantages over cell-based immunotherapies involving DCs. Accordingly, Dex-based phase I and II clinical trials have been conducted in advanced malignancies, showing the feasibility and safety of the approach, as well as the propensity of these nanovesicles to mediate T and NK cell–based immune responses in patients. This Review will evaluate the interactions of Dex with immune cells, their clinical progress, and the future of Dex immunotherapy for cancer

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“…Selective protein delivery or gene therapy approaches through exosomes are already ongoing in neurodegenerative and cardiovascular diseases, with quite exciting preclinical results (24,25). One of the first clinical trials based on exosome administration was performed again in cancer several years ago, with exosomes produced by dendritic cells (Dexosomes), exploited to shuttle antigenic determinants of immune response, and to immunize patients in the context of cancer vaccines (26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

TNF-Related Apoptosis-Inducing Ligand (TRAIL)–Armed Exosomes Deliver Proapoptotic Signals to Tumor Site

Rivoltini

Chiodoni

Squarcina

et al. 2016

Clinical Cancer Research

163

120

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Purpose: Exosomes deliver signals to target cells and could thus be exploited as an innovative therapeutic tool. We investigated the ability of membrane TRAIL-armed exosomes to deliver proapoptotic signals to cancer cells and mediate growth inhibition in different tumor models.Experimental Methods and Results: K562 cells, transduced with lentiviral human membrane TRAIL, were used for the production of TRAIL þ exosomes, which were studied by nanoparticle tracking analysis, cytofluorimetry, immunoelectronmicroscopy, Western blot, and ELISA. In vitro, TRAIL þ exosomes induced more pronounced apoptosis (detected by Annexin V/ propidium iodide and activated caspase-3) in TRAIL-death receptor (DR)5 þ cells (SUDHL4 lymphoma and INT12 melanoma), with respect to the DR5 À DR4 þ KMS11 multiple myeloma. Intratumor injection of TRAIL þ exosomes, but not mock exosomes, induced growth inhibition of SUDHL4 (68%) and INT12 (51%), and necrosis in KMS11 tumors. After rapid blood clearance, systemically administered TRAIL þ exosomes accumulated in the liver, lungs, and spleen and homed to the tumor site, leading to a significant reduction of tumor growth (58%) in SUDHL4-bearing mice. The treatment of INT12-bearing animals promoted tumor necrosis and a not statistically significant tumor volume reduction. In KMS11-bearing mice, despite massive perivascular necrosis, no significant tumor growth inhibition was detected.Conclusions: TRAIL-armed exosomes can induce apoptosis in cancer cells and control tumor progression in vivo. Therapeutic efficacy was particularly evident in intratumor setting, while depended on tumor model upon systemic administration. Thanks to their ability to deliver multiple signals, exosomes thus represent a promising therapeutic tool in cancer.

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Dendritic Cell–Derived Exosomes as Immunotherapies in the Fight against Cancer

Cited by 238 publications

References 50 publications

The exosomes in tumor immunity

The exosomes in tumor immunity

Dendritic cell–derived exosomes for cancer therapy

TNF-Related Apoptosis-Inducing Ligand (TRAIL)–Armed Exosomes Deliver Proapoptotic Signals to Tumor Site

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