Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells

F André, N Chaput, NEC Schartz, C Flament… - The Journal of …, 2004 - journals.aai.org
F André, N Chaput, NEC Schartz, C Flament, N Aubert, J Bernard, F Lemonnier, G Raposo…
The Journal of Immunology, 2004journals.aai.org
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 …
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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