Exosomes as potent cell-free peptide-based vaccine. II. Exosomes in CpG adjuvants efficiently prime naive Tc1 lymphocytes leading to tumor rejection.
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.
Chaput
Nathalie
N
Unité d'Immunologie, ERM0208 Institut National de la Santé et de la Recherche Médicale, Department of Clinical Biology, Institut Gustave Roussy, Villejuif, France.
Schartz
Nöel E C
NE
André
Fabrice
F
Taïeb
Julien
J
Novault
Sophie
S
Bonnaventure
Pierre
P
Aubert
Nathalie
N
Bernard
Jacky
J
Lemonnier
François
F
Merad
Miriam
M
Adema
Gosse
G
Adams
Malcolm
M
Ferrantini
Maria
M
Carpentier
Antoine F
AF
Escudier
Bernard
B
Tursz
Thomas
T
Angevin
Eric
E
Zitvogel
Laurence
L
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
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