MP98-06 EFFICACY OF RECOMBINANT BACILLE CALMETTE-GUÉRIN SECRETING INTERLEUKIN-15 AGAINST BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology V1 Apr 2017MP98-06 EFFICACY OF RECOMBINANT BACILLE CALMETTE-GUÉRIN SECRETING INTERLEUKIN-15 AGAINST BLADDER CANCER Ario Takeuchi, Masaki Shiota, Katsunori Tatsugami, and Masatoshi Eto Ario TakeuchiArio Takeuchi More articles by this author , Masaki ShiotaMasaki Shiota More articles by this author , Katsunori TatsugamiKatsunori Tatsugami More articles by this author , and Masatoshi EtoMasatoshi Eto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.3071AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been used for the treatment of bladder cancer for almost 40 years, although the antitumor effector mechanisms remain elusive. Recent our study demonstrated interleukin (IL)-17 produced by γδT cells plays a key role in the recruitment of neutrophlis to the bladder after BCG instillation, which is important for the antitumor activity against bladder tumor. And, other studies reported that IL-15 plays an important role in neutrophil migration during inflammation. In the present study, we constructed a recombinant BCG expressing the fusion protein of IL-15 (BCG-IL-15) and examined the efficacy of BCG-IL-15 in providing protection against bladder cancer. METHODS Six-week-old female C57BL/6 (B6) mice or CδKO mice (B6 background) were intravesically inoculated with 2 x 105 bladder tumor cells (MB49 cells) on day 0. On day 1, 8, 15, and 22 after tumor implantation, mice were inoculated intravesically with either 2 x 106 BCG-IL-15, BCG or PBS weekly. RESULTS BCG-IL-15 treatment prolonged the survival of mice inoculated with bladder cancer cells, compared with BCG treatmnet. We analyzed the effector cells (neutrophils and γδ T cells), which were reported to play key roles in the anti-tumor response. We found infiltration of neutrophil and γδ T cells were significantly elevated in BCG-IL-15 treated mice. Moreover, we confirmed the importance of neutrophils and γδT cells in antitumor effect of BCG-IL-15 therapy by depleting neutrophils with anti Gr-1 antibody and using γδ T cells KO mice (Cδ KO mice). To examine whether IL-17 production was induced by intravesical instillations of BCG-IL-15, we measured vesical IL-17 production by ELISA. IL-17 production after BCG-IL-15 treatment was significantly increased. Moreover, although we previously reported TCRγδand CD25-positive population were IL-17 producing γδT cells, the percentage and the absolute number of TCRγδ and CD25-positive cells of BCG-IL-15-treated mice significantly increased. CONCLUSIONS These results suggested that IL-17 produced by γδT cells and chemokines (MIP-2 and MIP-1) induced by BCG-IL-15 played a key role in the recruitment of neutrophlis to the bladder wall. And we believe BCG-IL-15 can become one of the promising drugs for the non muscle invasive bladder cancer. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1313-e1314 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ario Takeuchi More articles by this author Masaki Shiota More articles by this author Katsunori Tatsugami More articles by this author Masatoshi Eto More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...