Exosomes as potent cell-free peptide-based vaccine. II. Exosomes in CpG adjuvants efficiently prime naive Tc1 lymphocytes leading to tumor rejection.

Abstract

Ideal vaccines should be stable, safe, molecularly defined, and out-of-shelf reagents efficient at triggering effector and memory Ag-specific T cell-based immune responses. Dendritic cell-derived exosomes could be considered as novel peptide-based vaccines because exosomes harbor a discrete set of proteins, bear functional MHC class I and II molecules that can be loaded with synthetic peptides of choice, and are stable reagents that were safely used in pioneering phase I studies. However, we showed in part I that exosomes are efficient to promote primary MHC class I-restricted effector CD8(+) T cell responses only when transferred onto mature DC in vivo. In this work, we bring evidence that among the clinically available reagents, Toll-like receptor 3 and 9 ligands are elective adjuvants capable of triggering efficient MHC-restricted CD8(+) T cell responses when combined to exosomes. Exosome immunogenicity across species allowed to verify the efficacy of good manufactory procedures-manufactured human exosomes admixed with CpG oligonucleotides in prophylactic and therapeutic settings of melanoma in HLA-A2 transgenic mice. CpG adjuvants appear to be ideal adjuvants for exosome-based cancer vaccines.

• Authors: Nathalie Chaput, Nöel E C Schartz, Fabrice André, Julien Taïeb, Sophie Novault, Pierre Bonnaventure, Nathalie Aubert, Jacky Bernard, François Lemonnier, Miriam Merad, Gosse Adema, Malcolm Adams, Maria Ferrantini, Antoine F Carpentier, Bernard Escudier, Thomas Tursz, Eric Angevin, Laurence Zitvogel
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 172 Issue 4 Pg. 2137-46 (Feb 15 2004) ISSN: 0022-1767 [Print] United States
• PMID: 14764679 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• CPG-oligonucleotide
• Cancer Vaccines
• DNA-Binding Proteins
• HLA-A2 Antigen
• Ligands
• Membrane Glycoproteins
• Neoplasm Proteins
• Oligodeoxyribonucleotides
• PMEL protein, human
• Pmel protein, mouse
• RNA, Double-Stranded
• Receptors, Cell Surface
• TLR3 protein, human
• TLR9 protein, human
• Tlr9 protein, mouse
• Toll-Like Receptor 3
• Toll-Like Receptor 9
• Toll-Like Receptors
• Vaccines, Subunit
• gp100 Melanoma Antigen

Topics

• Adjuvants, Immunologic (administration & dosage, metabolism)
• Animals
• Cancer Vaccines (administration & dosage, immunology)
• Cell-Free System (immunology, transplantation)
• CpG Islands (immunology)
• DNA-Binding Proteins (metabolism)
• Endosomes (immunology, transplantation)
• Graft Rejection (immunology)
• HLA-A2 Antigen (biosynthesis, genetics, immunology)
• Humans
• Interphase (immunology)
• Ligands
• Melanoma, Experimental (immunology, prevention & control)
• Membrane Glycoproteins (biosynthesis, genetics, immunology, metabolism)
• Mice
• Neoplasm Proteins (biosynthesis, genetics, immunology)
• Oligodeoxyribonucleotides (administration & dosage, immunology, metabolism)
• RNA, Double-Stranded (immunology)
• Receptors, Cell Surface (metabolism)
• T-Lymphocytes, Cytotoxic (cytology, immunology, metabolism)
• T-Lymphocytes, Regulatory (cytology, immunology)
• Toll-Like Receptor 3
• Toll-Like Receptor 9
• Toll-Like Receptors
• Vaccines, Subunit (administration & dosage, immunology)
• gp100 Melanoma Antigen