title: 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.affiliation: Unité d'Immunologie, ERM0208 Institut National de la Santé et de la Recherche Médicale, Department of Clinical Biology, Institut Gustave Roussy, Villejuif, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chaput
authors.forename: Nöel E C
authors.initials: NE
authors.lastname: Schartz
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.forename: Julien
authors.initials: J
authors.lastname: Taïeb
authors.forename: Sophie
authors.initials: S
authors.lastname: Novault
authors.forename: Pierre
authors.initials: P
authors.lastname: Bonnaventure
authors.forename: Nathalie
authors.initials: N
authors.lastname: Aubert
authors.forename: Jacky
authors.initials: J
authors.lastname: Bernard
authors.forename: François
authors.initials: F
authors.lastname: Lemonnier
authors.forename: Miriam
authors.initials: M
authors.lastname: Merad
authors.forename: Gosse
authors.initials: G
authors.lastname: Adema
authors.forename: Malcolm
authors.initials: M
authors.lastname: Adams
authors.forename: Maria
authors.initials: M
authors.lastname: Ferrantini
authors.forename: Antoine F
authors.initials: AF
authors.lastname: Carpentier
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.forename: Thomas
authors.initials: T
authors.lastname: Tursz
authors.forename: Eric
authors.initials: E
authors.lastname: Angevin
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002474:Cell-Free System / Q000276:immunology / Q000637:transplantation; D018899:CpG Islands / Q000276:immunology; D004268:DNA-Binding Proteins / Q000378:metabolism; D011992:Endosomes / Q000276:immunology* / Q000637:transplantation; D006084:Graft Rejection / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007399:Interphase / Q000276:immunology; D008024:Ligands; D008546:Melanoma, Experimental / Q000276:immunology* / Q000517:prevention & control; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*; D058951:gp100 Melanoma Antigen
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; D015789:HLA-A2 Antigen; D008024:Ligands; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; C548637:PMEL protein, human; C548642:Pmel protein, mouse; D012330:RNA, Double-Stranded; D011956:Receptors, Cell Surface; C495344:TLR3 protein, human; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D022223:Vaccines, Subunit; D058951:gp100 Melanoma Antigen