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Mahaweni NM, Kaijen-Lambers ME, Dekkers J, et al. Tumour-derived exosomes as antigen delivery carriers in dendritic cell-based immunotherapy for malignant mesothelioma. J Extracell Vesicles. 2013;2doi: 10.3402/jev.v2i0.22492.
Mahaweni, N. M., Kaijen-Lambers, M. E., Dekkers, J., Aerts, J. G., & Hegmans, J. P. (2013). Tumour-derived exosomes as antigen delivery carriers in dendritic cell-based immunotherapy for malignant mesothelioma. Journal of extracellular vesicles, 2. https://doi.org/10.3402/jev.v2i0.22492
Mahaweni, Niken M, et al. "Tumour-derived exosomes as antigen delivery carriers in dendritic cell-based immunotherapy for malignant mesothelioma." Journal of extracellular vesicles vol. 2 (2013). doi: https://doi.org/10.3402/jev.v2i0.22492
Mahaweni NM, Kaijen-Lambers ME, Dekkers J, Aerts JG, Hegmans JP. Tumour-derived exosomes as antigen delivery carriers in dendritic cell-based immunotherapy for malignant mesothelioma. J Extracell Vesicles. 2013 Oct 24;2. doi: 10.3402/jev.v2i0.22492. eCollection 2013. PMID: 24223258; PMCID: PMC3823268.
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J Extracell Vesicles. 2013 Oct 24;2. doi: 10.3402/jev.v2i0.22492. eCollection 2013.

Tumour-derived exosomes as antigen delivery carriers in dendritic cell-based immunotherapy for malignant mesothelioma.

Journal of extracellular vesicles

Niken M Mahaweni, Margaretha E H Kaijen-Lambers, Jacqueline Dekkers, Joachim G J V Aerts, Joost P J J Hegmans

Affiliations

  1. Department of Pulmonary Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

PMID: 24223258 PMCID: PMC3823268 DOI: 10.3402/jev.v2i0.22492

Abstract

BACKGROUND: In 2001, it was postulated that tumour-derived exosomes could be a potent source of tumour-associated antigens (TAA). Since then, much knowledge is gained on their role in tumorigenesis but only very recently tumour-derived exosomes were used in dendritic cell (DC)-based immunotherapy. For this, DCs were cultured ex-vivo and loaded with exosomes derived from immunogenic tumours such as melanoma or glioma and re-administrated to induce anti-tumour responses in primary and metastatic tumour mouse models. In contrast, malignant mesothelioma (MM) is a non-immunogenic tumour and because only a few mesothelioma-specific TAA are known to date, we investigated whether mesothelioma-derived exosomes could be used as antigen source in DC-based immunotherapy.

METHODS: Mouse MM AB1 cells were used to generate tumour lysate and tumour-derived exosomes. Tumour lysate was generated by 5 cycles of freeze-thawing followed by sonication of AB1 cells. Tumour exosomes were collected from the AB1 cell culture supernatant and followed a stepwise ultracentrifugation. Protein quantification and electron microscopy were performed to determine the protein amount and to characterise their morphology. To test whether MM derived exosomes are immunogenic and able to stimulate an anti-tumoral response, BALB/c mice were injected with a lethal dose of AB1 tumour cells at day 0, followed by intraperitoneal injection of a single dose of DCs loaded with tumour exosomes, DCs loaded with tumour lysate, or phosphate buffered saline (PBS), at day 7.

RESULTS: Mice which received tumour exosome-loaded DC immunotherapy had an increased median and overall survival compared to mice which received tumour lysate-loaded DC or PBS.

CONCLUSION: In this study, we showed that DC immunotherapy loaded with tumour exosomes derived from non-immunogenic tumours improved survival of tumour bearing mice.

Keywords: dendritic cell(s); exosomes; immunotherapy; mesothelioma; tumour antigens

References

  1. J Neurooncol. 2011 Sep;104(3):659-67 - PubMed
  2. Lancet. 2002 Jul 27;360(9329):295-305 - PubMed
  3. J Immunol Methods. 1999 Feb 1;223(1):77-92 - PubMed
  4. Vaccine. 2002 Dec 19;20 Suppl 4:A28-31 - PubMed
  5. Traffic. 2008 Jun;9(6):871-81 - PubMed
  6. Curr Oncol. 2009 May;16(3):46-9 - PubMed
  7. Am J Respir Crit Care Med. 2005 May 15;171(10):1168-77 - PubMed
  8. PLoS One. 2012;7(3):e33330 - PubMed
  9. Eur Urol. 2011 May;59(5):823-31 - PubMed
  10. Am J Pathol. 2004 May;164(5):1807-15 - PubMed
  11. J Biochem. 2006 Jul;140(1):13-21 - PubMed
  12. Nat Med. 2001 Mar;7(3):297-303 - PubMed
  13. FASEB J. 2009 Jun;23(6):1858-68 - PubMed
  14. Am J Respir Crit Care Med. 2010 Jun 15;181(12):1383-90 - PubMed
  15. Anal Chem. 1991 Mar 1;63(5):408-12 - PubMed
  16. Cancer Res. 2007 Aug 1;67(15):7458-66 - PubMed
  17. Int J Oncol. 2010 Jan;36(1):133-40 - PubMed
  18. Curr Protoc Cell Biol. 2006 Apr;Chapter 3:Unit 3.22 - PubMed
  19. Am J Respir Cell Mol Biol. 2004 Jul;31(1):114-21 - PubMed
  20. Clin Dev Immunol. 2011;2011:842849 - PubMed

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