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* Unité d’Immunologie, ERM0208 Institut National de la Santé et de la Recherche Médicale, Department of Clinical Biology, Institut Gustave Roussy, Villejuif, France;
Centre Jean Godinot, Reims, France;
Unité d’Immunologie Cellulaire Antivirale, Institut Pasteur, Paris, France;
Service de Dermatologie 2, AP-HP Saint Louis, Paris, France;
¶ Stanford University, Stanford Blood Center, Stanford, CA 04304;
|| Laboratory of Virology, Istituto Superiore di Sanita, Rome, Italy;
# Department of Tumor Immunology, University Hospital Nijmegen, Nijmegen, The Netherlands;
** Department of Medical Oncology, Velindre Hospital NHS Trust, Cardiff, United Kingdom; and
Service de Neurologie, AP-HP Pitié Salpétrière, Paris, France
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.
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