TY - JOUR
T1 - Antitumor activity of recombinant Bacille Calmette-Guérin secreting interleukin-15-Ag85B fusion protein against bladder cancer
AU - Takeuchi, Ario
AU - Eto, Masatoshi
AU - Tatsugami, Katsunori
AU - Shiota, Masaki
AU - Yamada, Hisakata
AU - Kamiryo, Yoriyuki
AU - Dejima, Takashi
AU - Kashiwagi, Eiji
AU - Kiyoshima, Keijiro
AU - Inokuchi, Junichi
AU - Takahashi, Ryosuke
AU - Yokomizo, Akira
AU - Ohara, Naoya
AU - Yoshikai, Yasunobu
N1 - Funding Information:
This work was supported by Kakenhi grants ( 26861274 ) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan ( MEXT ), Japan.
Publisher Copyright:
© 2016 Elsevier B.V. All rights reserved.
PY - 2016/6
Y1 - 2016/6
N2 - 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.
AB - 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.
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U2 - 10.1016/j.intimp.2016.03.007
DO - 10.1016/j.intimp.2016.03.007
M3 - Article
C2 - 27093372
AN - SCOPUS:84963825566
VL - 35
SP - 327
EP - 331
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
ER -
