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Biotechnology Letters

, Volume 38, Issue 11, pp 1857–1866 | Cite as

Exosomes derived from tumor cells genetically modified to express Mycobacterium tuberculosis antigen: a novel vaccine for cancer therapy

  • Yoshiyuki KoyamaEmail author
  • Tomoko Ito
  • Aya Hasegawa
  • Masazumi Eriguchi
  • Toshio Inaba
  • Takahiro Ushigusa
  • Kikuya Sugiura
Original Research Paper

Abstract

Objectives

To examine the potential of exosomes derived from the tumor cells, which had been genetically modified to express a Mycobacterium tuberculosis antigen, as a cancer vaccine aimed at overcoming the weak immunogenicity of tumor antigens.

Results

We transfected B16 melanoma cells with a plasmid encoding the M. tuberculosis antigen, early secretory antigenic target-6 (ESAT-6). The secreted exosomes bearing both tumor-associated antigens and the pathogenic antigen (or their epitopes) were collected. When the exosomes were injected into foot pads of mice, they significantly (p < 0.05) evoked cellular immunity against both ESAT-6, and B16 tumor cells. Intra-tumoral injection of the exosomes significantly suppressed (p < 0.001) tumor growth in syngeneic B16 tumor-bearing mice, while the exosomes derived from the non-transfected B16 cells showed no effect on tumor growth, although both exosomes should have similar tumor antigens.

Conclusions

Exosomes bearing both tumor antigens and the M. tuberculosis antigen (or their epitopes) have a high potential as a candidate for cancer vaccine to overcome the immune escape by tumor cells.

Keywords

Cancer vaccine Early secretory antigenic target-6 (ESAT-6) Exogenous danger signal Exosomes Mycobacterium tuberculosis antigen Neoantigens Neoepitopes 

Notes

Acknowledgments

Authors are grateful to Prof. Hideo Nariuchi for his kind and important advices. This work was supported by JSPS KAKENHI Grant Numbers 25350555 and 16K01394.

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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.Japan Anti-tuberculosis AssociationShin-Yamanote HospitalTokyoJapan
  2. 2.Graduate School of Life and Environmental SciencesOsaka Prefecture UniversityOsakaJapan
  3. 3.Kannai Animal ClinicYokohamaJapan

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