Cancer Immunology, Immunotherapy

, Volume 53, Issue 3, pp 234–239 | Cite as

Exosome-based immunotherapy

  • Nathalie Chaput
  • Julien Taïeb
  • Noël E. C. Schartz
  • Fabrice André
  • Eric Angevin
  • Laurence Zitvogel


Exosomes are small membrane vesicles originating from late endosomes and secreted by hematopoietic and epithelial cells in culture. Exosome proteic and lipid composition is unique and might shed some light into exosome biogenesis and function. Exosomes secreted from professional antigen-presenting cells (i.e., B lymphocytes and dendritic cells) are enriched in MHC class I and II complexes, costimulatory molecules, and hsp70–90 chaperones, and have therefore been more extensively studied for their immunomodulatory capacities in vitro and in vivo. This review will present the main biological features pertaining to tumor or DC-derived exosomes, will emphasize their immunostimulatory function, and will discuss their implementation in cancer immunotherapy.


Exosomes Cross-presentation MHC complexes Tumor Immunotherapy 



antigen-presenting cell


active specific immunotherapy


cytotoxic T lymphocyte


dendritic cell


follicular dendritic cell


monocyte-derived dendritic cell


good manufacturing procedure


human leukocyte antigen


heat shock protein


major histocompatibility complex


multivesicular body


ascitis-derived exosomes


DC-derived exosome


tumor cell–derived exosome


  1. 1.
    Denzer K, Kleijmeer MJ, Heijnen HF, Stoorvogel W, Geuze HJ (2000) Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci 113:3365–3374PubMedGoogle Scholar
  2. 2.
    Denzer K, van Eijk M, Kleijmeer MJ, Jakobson E, de Groot C, Geuze HJ (2000) Follicular dendritic cells carry MHC class II-expressing microvesicles at their surface. J Immunol 165:1259–1265PubMedGoogle Scholar
  3. 3.
    Quah B, O’Neill HC (2000) The application of dendritic cell-derived exosomes in tumour immunotherpy. Cancer Biother Radiopharm 15:185–194PubMedGoogle Scholar
  4. 4.
    André F, Schartz NE, Movassagh M, Flament C, Pautier P, Morice P, Pomel C, Lhomme C, Escudier B, Le Chevalier T, Tursz T, Amigorena S, Raposo G, Angevin E, Zitvogel L (2002) Malignant effusions and immunogenic tumor derived-exosomes. Lancet 360:295–305CrossRefPubMedGoogle Scholar
  5. 5.
    Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, Ricciardi-Castagnoli P, Raposo G, Amigorena S (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med 4:594–600PubMedGoogle Scholar
  6. 6.
    Wolfers J, Lozier A, Raposo G, Regnault A, Thery C, Masurier C, Flament C, Pouzieux S, Faure F, Tursz T, Angevin E, Amigorena S, Zitvogel L (2001) Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med 7:297–303PubMedGoogle Scholar
  7. 7.
    Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C (1987) Vesicle formation during reticulocyte maturation: association of plasma membrane activities with released vesicles (exosomes). J Biol Chem 262:9412–9420PubMedGoogle Scholar
  8. 8.
    Raposo G, Tenza D, Mecheri S, Peronet R, Bonnerot C, Desaymard C (1997) Accumulation of major histocompatibility complex class II molecules in mast cell secretory granules and their release upon degranulation. Mol Biol Cell 8:2631–2645PubMedGoogle Scholar
  9. 9.
    Escola JM, Kleijmeer MJ, Stoorvogel W, Griffith JM, Yoshie O, Geuze HJ (1998) Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem 273:20121–20127CrossRefPubMedGoogle Scholar
  10. 10.
    Arnold PY, Mannie MD (1999) Vesicles bearing MHC class II molecules mediate transfer of antigen-presenting cells to CD4+ cells. Eur J Immunol 29:1363–1373CrossRefPubMedGoogle Scholar
  11. 11.
    Heijnen IA, van Vugt MJ, Fanger NA, Graziano RF, de Wit TP, Hofhuis FM, Guyre PM, Capel PJ, Verbeek JS, van de Winkel JG (1996) Antigen targeting to myeloid-specific human Fc gamma RI/CD64 triggers enhanced antibody responses in transgenic mice. J Clin Investig 97:331–338Google Scholar
  12. 12.
    Hess C, Sadallah S, Hefti A, Landmann R, Schifferli JA (1999) Ectosomes released by human neutrophils are specialized functional units. J Immunol 163:4564–4573PubMedGoogle Scholar
  13. 13.
    Patel DM, Arnold PY, White GA, Nardella JP, Mannie MD (1999) Class II MHC/peptide complexes are released from APC and are acquired by T cell responders during specific antigen recognition. J Immunol 163:5201–5210PubMedGoogle Scholar
  14. 14.
    Geminard C, Nault F, Johnstone RM, Vidal M (2001) Characteristics of the Interaction between Hsc70 and the transferrin receptor in exosomes released during reticulocyte maturation. J Biol Chem 276:9910–9916CrossRefPubMedGoogle Scholar
  15. 15.
    Skokos D, Le Panse S, Villa I, Rousselle JC, Peronet R, David B, Namane A, Mecheri S (2001) Mast cell-dependent B and T lymphocyte activation is mediated by the secretion of immunologically active exosomes. J Immunol 166:868–876PubMedGoogle Scholar
  16. 16.
    Thery C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2:569–579PubMedGoogle Scholar
  17. 17.
    Yang S, Kittlesen D, Slingluff CL Jr, Vervaert CE, Seigler HF, Darrow TL (2000) Dendritic cells infected with a vaccinia vector carrying the human gp100 gene simultaneously present multiple specificities and elicit high-affinity T cells reactive to multiple epitopes and restricted by HLA-A2 and -A3. J Immunol 164(8):4204–4211PubMedGoogle Scholar
  18. 18.
    Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 193:233–238PubMedGoogle Scholar
  19. 19.
    Chaput N, André F, Schartz NEC, Escudier B, Turz T, Angevin E, Zitvogel L (2003) Proc Am Assoc Cancer Res 44:A4746Google Scholar
  20. 20.
    Théry C, Duban L, Segura E, Véron P, Lantz O, Amigorena S (2002) Exosomes activate naive CD4+ T cells by transfer of MHC/peptide complexes to dendritic cells. Nat Immunol 3:1156–1162CrossRefPubMedGoogle Scholar
  21. 21.
    Lamparski H, Metha-Damani A, Yao J, Patel S, Hsu D, Ruegg C, Le Pecq J (2002) Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Meth 270(2):211Google Scholar
  22. 22.
    H. Pêche (2001) Club Francophone Des Cellules Dendritiques, p 31 (Abstract C08)Google Scholar
  23. 23.
    E. Angevin (2002) 7th International Symposium on Dendritic Cells, p 28 (Abstract 20)Google Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Nathalie Chaput
    • 1
  • Julien Taïeb
    • 1
    • 2
  • Noël E. C. Schartz
    • 1
    • 3
  • Fabrice André
    • 1
    • 4
  • Eric Angevin
    • 1
  • Laurence Zitvogel
    • 1
  1. 1.ERIT-M 02-08 INSERM, Department of Clinical BiologyInstitut Gustave Roussy (IGR)VillejuifFrance
  2. 2.Department of Hepatology and GastroenterologyPitié Salpétrière HospitalParisFrance
  3. 3.Department of DermatologySaint Louis HospitalParisFrance
  4. 4.Department of Medical OncologyInstitut Gustave Roussy (IGR)VillejuifFrance

Personalised recommendations