Exosomes as Potent Cell-Free Peptide-Based Vaccine. I. Dendritic Cell-Derived Exosomes Transfer Functional MHC Class I/Peptide Complexes to Dendritic Cells
Abstract
Current immunization protocols in cancer patients involve CTL-defined tumor peptides. Mature dendritic cells (DC) are the most potent APCs for the priming of naive CD8+ T cells, eventually leading to tumor eradication. Because DC can secrete MHC class I-bearing exosomes, we addressed whether exosomes pulsed with synthetic peptides could subserve the DC function consisting in MHC class I-restricted, peptide-specific CTL priming in vitro and in vivo. The priming of CTL restricted by HLA-A2 molecules and specific for melanoma peptides was performed: 1) using in vitro stimulations of total blood lymphocytes with autologous DC pulsed with GMP-manufactured autologous exosomes in a series of normal volunteers; 2) in HLA-A2 transgenic mice (HHD2) using exosomes harboring functional HLA-A2/Mart1 peptide complexes. In this study, we show that: 1) DC release abundant MHC class I/peptide complexes transferred within exosomes to other naive DC for efficient CD8+ T cell priming in vitro; 2) exosomes require nature’s adjuvants (mature DC) to efficiently promote the differentiation of melanoma-specific effector T lymphocytes producing IFN-γ (Tc1) effector lymphocytes in HLA-A2 transgenic mice (HHD2). These data imply that exosomes might be a transfer mechanism of functional MHC class I/peptide complexes to DC for efficient CTL activation in vivo.
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Extracellular vesicles are secreted by both normal and cancerous cells as a means of cell-to-cell communication.
“These vesicles are secreted by both normal cells and cancerous cells as means of cell-to-cell communication [2-5].”
From Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies (2013) · cites this paper as [4]
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- Authors
- André, F., Chaput, N., Schartz, N. E. C., Flament, C., Aubert, N., Bernard, J., Lemonnier, F., Raposo, G., Escudier, B., Hsu, D.-H., Tursz, T., Amigorena, S., Angevin, E., & Zitvogel, L.
- Affiliations
- Unité d’Immunologie, ERM0208 Institut National de la Santé et de la Recherche Médicale, Department of Clinical Biology, Institut Gustave Roussy , Villejuif ,
- Inserm (FR)
- Institut Jean Godinot (FR)
- Unité d’Immunologie Cellulaire Antivirale, Institut Pasteur , Paris ,
- Unité Mixte de Recherche 144 Centre National de la Recherche Scientifique Institut Curie , Paris ,
- Anosys, Inc. , Menlo Park, CA 94025
- Institut National de la Santé et de la Recherche Médicale Unité 520, Institut Curie , Paris ,
- Corresponding author
- Chaput, Nathalie
- Flament, Caroline
- Escudier, Bernard
- Tursz, Thomas
- Angevin, Eric
- Zitvogel, Laurence
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-02
- Volume
- 172
- Issue
- 4
- Pages
- 2126-2136
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1804501722
- Cited by
- 496
- References
- 3
- Citations by year
- 2026: 11 · 2025: 22 · 2024: 31 · 2023: 20 · 2022: 41 · 2021: 33 · 2020: 32 · 2019: 24 · 2018: 24 · 2017: 23 · 2016: 21 · 2015: 22 · 2014: 19 · 2013: 17 · 2012: 22
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- exosomes, dendritic cells, peptide-MHC complex, cell-free vaccine, CTL priming, HLA-A2, Melan-A, CD8+ T cells, T cell activation, exosome transfer, interferon-gamma, cancer immunotherapy
- MeSH terms
- Animals, Antigens, Neoplasm, Cell Differentiation, Cell-Free System, Cells, Cultured, Cytotoxicity, Immunologic, Dendritic Cells, Humans, Interphase, Lymphocyte Activation, Mice, Transgenic, Neoplasm Proteins, Endosomes, T-Lymphocytes, Cytotoxic, Histocompatibility Antigens Class I, HLA-A2 Antigen, Antigen Presentation, CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, Cancer Vaccines, Vaccines, Subunit, Cell Line, Tumor, Mice, MART-1 Antigen
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