Display options
Cite
Grandi A, Tomasi M, Zanella I, et al. Synergistic Protective Activity of Tumor-Specific Epitopes Engineered in Bacterial Outer Membrane Vesicles. Front Oncol. 2017;7:253doi: 10.3389/fonc.2017.00253.
Grandi, A., Tomasi, M., Zanella, I., Ganfini, L., Caproni, E., Fantappiè, L., Irene, C., Frattini, L., Isaac, S. J., König, E., Zerbini, F., Tavarini, S., Sammicheli, C., Giusti, F., Ferlenghi, I., Parri, M., & Grandi, G. (2017). Synergistic Protective Activity of Tumor-Specific Epitopes Engineered in Bacterial Outer Membrane Vesicles. Frontiers in oncology, 7253. https://doi.org/10.3389/fonc.2017.00253
Grandi, Alberto, et al. "Synergistic Protective Activity of Tumor-Specific Epitopes Engineered in Bacterial Outer Membrane Vesicles." Frontiers in oncology vol. 7 (2017): 253. doi: https://doi.org/10.3389/fonc.2017.00253
Grandi A, Tomasi M, Zanella I, Ganfini L, Caproni E, Fantappiè L, Irene C, Frattini L, Isaac SJ, König E, Zerbini F, Tavarini S, Sammicheli C, Giusti F, Ferlenghi I, Parri M, Grandi G. Synergistic Protective Activity of Tumor-Specific Epitopes Engineered in Bacterial Outer Membrane Vesicles. Front Oncol. 2017 Nov 07;7:253. doi: 10.3389/fonc.2017.00253. eCollection 2017. PMID: 29164053; PMCID: PMC5681935.
Copy Download .nbib Format: NLM
Share it on

Front Oncol. 2017 Nov 07;7:253. doi: 10.3389/fonc.2017.00253. eCollection 2017.

Synergistic Protective Activity of Tumor-Specific Epitopes Engineered in Bacterial Outer Membrane Vesicles.

Frontiers in oncology

Alberto Grandi, Michele Tomasi, Ilaria Zanella, Luisa Ganfini, Elena Caproni, Laura Fantappiè, Carmela Irene, Luca Frattini, Samine J Isaac, Enrico König, Francesca Zerbini, Simona Tavarini, Chiara Sammicheli, Fabiola Giusti, Ilaria Ferlenghi, Matteo Parri, Guido Grandi

Affiliations

  1. Toscana Life Sciences, Siena, Italy.
  2. Centre for Integrative Biology (CIBIO), University of Trento, Trento, Italy.
  3. GlaxoSmithKline Vaccines (GSK) Vaccines, Siena, Italy.

PMID: 29164053 PMCID: PMC5681935 DOI: 10.3389/fonc.2017.00253

Abstract

INTRODUCTION: Bacterial outer membrane vesicles (OMVs) are naturally produced by all Gram-negative bacteria and, thanks to their plasticity and unique adjuvanticity, are emerging as an attractive vaccine platform. To test the applicability of OMVs in cancer immunotherapy, we decorated them with either one or two protective epitopes present in the B16F10EGFRvIII cell line and tested the protective activity of OMV immunization in C57BL/6 mice challenged with B16F10EGFRvIII.

MATERIALS AND METHODS: The 14 amino acid B cell epitope of human epidermal growth factor receptor variant III (EGFRvIII) and the mutation-derived CD4+ T cell neo-epitope of

RESULTS: Immunization with engineered EGFRvIII-OMVs induced a strong inhibition of tumor growth after B16F10EGFRvIII challenge. Furthermore, mice immunized with engineered OMVs carrying both EGFRvIII and M30 epitopes were completely protected from tumor challenge. Immunization was accompanied by induction of high anti-EGFRvIII antibody titers, M30-specific T cells, and infiltration of CD4+ and CD8+ T cells at the tumor site.

CONCLUSION: OMVs can be decorated with tumor antigens and can elicit antigen-specific, protective antitumor responses in immunocompetent mice. The synergistic protective activity of multiple epitopes simultaneously administered with OMVs makes the OMV platform particularly attractive for cancer immunotherapy.

Keywords: BALB/c-CT26 cancer mouse model; EGRRvIII; bacterial outer membrane vesicles; cancer immunotherapy; cancer neoepitopes; precision medicine

References

  1. Biotechnol Adv. 2017 Sep;35(5):565-574 - PubMed
  2. Nature. 2015 Apr 30;520(7549):692-6 - PubMed
  3. J Bacteriol. 1999 Aug;181(16):4725-33 - PubMed
  4. Mol Cell Proteomics. 2017 Jul;16(7):1348-1364 - PubMed
  5. Mol Microbiol. 2009 Jun;72(6):1395-407 - PubMed
  6. Vaccine. 2009 Nov 12;27(48):6748-54 - PubMed
  7. Science. 2015 Apr 3;348(6230):124-8 - PubMed
  8. Mol Microbiol. 2007 Jan;63(2):545-58 - PubMed
  9. Nature. 2016 Jun 01;534(7607):396-401 - PubMed
  10. J Bacteriol. 1998 Sep;180(18):4872-8 - PubMed
  11. Annu Rev Microbiol. 2010;64:163-84 - PubMed
  12. Immunol Rev. 2011 Jan;239(1):27-44 - PubMed
  13. J Biol Chem. 2004 Jan 16;279(3):2069-76 - PubMed
  14. N Engl J Med. 2014 Dec 4;371(23 ):2189-2199 - PubMed
  15. Hum Vaccin Immunother. 2012 Jul;8(7):953-5 - PubMed
  16. Clin Infect Dis. 2010 Mar 1;50 Suppl 2:S54-65 - PubMed
  17. J Immunol. 2007 Dec 1;179(11):7692-701 - PubMed
  18. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3099-104 - PubMed
  19. Expert Opin Biol Ther. 2017 Apr;17 (4):507-513 - PubMed
  20. Cell Microbiol. 2010 Mar;12(3):372-85 - PubMed
  21. J Extracell Vesicles. 2014 Aug 11;3:null - PubMed
  22. Science. 2015 Apr 3;348(6230):62-8 - PubMed
  23. Clin Cancer Res. 2003 Sep 15;9(11):4247-54 - PubMed
  24. PLoS One. 2014 Nov 26;9(11):e112802 - PubMed
  25. Science. 2015 Oct 9;350(6257):207-211 - PubMed
  26. Expert Rev Vaccines. 2012 Feb;11(2):133-44 - PubMed
  27. Science. 2013 Mar 29;339(6127):1546-58 - PubMed
  28. Proteomics. 2006 Mar;6(6):1856-66 - PubMed
  29. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4207-11 - PubMed
  30. Can J Microbiol. 1989 Jun;35(6):607-13 - PubMed
  31. Infect Immun. 2010 Sep;78(9):3822-31 - PubMed
  32. PLoS One. 2012;7(6):e35616 - PubMed
  33. Microbiol Mol Biol Rev. 2010 Mar;74(1):81-94 - PubMed

Publication Types