Antitumor activity of recombinant Bacille Calmette-Guérin secreting interleukin-15-Ag85B fusion protein against bladder cancer

Ario Takeuchi, Masatoshi Eto, Katsunori Tatsugami, Masaki Shiota, Hisakata Yamada, Yoriyuki Kamiryo, Takashi Dejima, Eiji Kashiwagi, Keijiro Kiyoshima, Junichi Inokuchi, Ryosuke Takahashi, Akira Yokomizo, Naoya Ohara, Yasunobu Yoshikai

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is used for the treatment of bladder cancer. The recruitment of neutrophlis to the bladder after BCG instillation exerts anti-tumor activity against bladder tumor. We have recently demonstrated that interleukin (IL)-17A produced by γδ T cells played a role in the recruitment of neutrophlis to the bladder after BCG instillation. IL-15 is known to play an important role in neutrophil migration during inflammation. We previously constructed a recombinant BCG strain expressing the fusion protein of IL-15 and Ag85B (BCG-IL-15) for prevention of Mycobacterium tuberculosis infection. Here we compared the efficacy of the BCG-IL-15 in protection against bladder cancer with that of rBCG-Ag85B (BCG). Six-week-old female C57BL/6 mice were inoculated with MB49 bladder tumor cells in the bladder and subsequently intravesically inoculated with BCG or BCG-IL-15. BCG-IL-15 treatment significantly prolonged survival of mice inoculated with bladder cancer cells compared with BCG treatment. Infiltration of neutrophils was significantly elevated in BCGB-IL-15 treated mice accompanied by increased chemokines (MIP-2 and MIP-1α) in the bladder. Thus, BCG-IL-15 exerted additive effect on Infiltration of neutrophils in the bladder. BCG-IL-15 may be a promising drug for non-muscle invasive bladder cancer.

Original languageEnglish
Pages (from-to)327-331
Number of pages5
JournalInternational Immunopharmacology
Volume35
DOIs
Publication statusPublished - Jun 2016

Keywords

  • BCG
  • Bladder cancer
  • Immunotherapy
  • Interleukin15
  • Mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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  • Cite this

    Takeuchi, A., Eto, M., Tatsugami, K., Shiota, M., Yamada, H., Kamiryo, Y., Dejima, T., Kashiwagi, E., Kiyoshima, K., Inokuchi, J., Takahashi, R., Yokomizo, A., Ohara, N., & Yoshikai, Y. (2016). Antitumor activity of recombinant Bacille Calmette-Guérin secreting interleukin-15-Ag85B fusion protein against bladder cancer. International Immunopharmacology, 35, 327-331. https://doi.org/10.1016/j.intimp.2016.03.007