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 language | English |
|---|---|
| Pages (from-to) | 327-331 |
| Number of pages | 5 |
| Journal | International Immunopharmacology |
| Volume | 35 |
| DOIs | |
| Publication status | Published - Jun 2016 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
- Pharmacology
Cite this
Antitumor activity of recombinant Bacille Calmette-Guérin secreting interleukin-15-Ag85B fusion protein against bladder cancer. / Takeuchi, Ario; Eto, Masatoshi; Tatsugami, Katsunori; Shiota, Masaki; Yamada, Hisakata; Kamiryo, Yoriyuki; Dejima, Takashi; Kashiwagi, Eiji; Kiyoshima, Keijiro; Inokuchi, Junichi; Takahashi, Ryosuke; Yokomizo, Akira; Ohara, Naoya; Yoshikai, Yasunobu.
In: International Immunopharmacology, Vol. 35, 06.2016, p. 327-331.Research output: Contribution to journal › Article
}
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
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.
UR - http://www.scopus.com/inward/record.url?scp=84963825566&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84963825566&partnerID=8YFLogxK
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 -