Antitumor activity of recombinant Bacille Calmette-Guérin secreting interleukin-15-Ag85B fusion protein against bladder cancer.
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.
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ario
A
Takeuchi
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: etom@uro.med.kyushu-u.ac.jp.
Masatoshi
M
Eto
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Katsunori
K
Tatsugami
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Masaki
M
Shiota
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Hisakata
H
Yamada
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yoriyuki
Y
Kamiryo
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Takashi
T
Dejima
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Eiji
E
Kashiwagi
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Keijiro
K
Kiyoshima
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Junichi
J
Inokuchi
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Ryosuke
R
Takahashi
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Akira
A
Yokomizo
Department of Oral Microbiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Naoya
N
Ohara
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Yasunobu
Y
Yoshikai
D000217:Acyltransferases / Q000235:genetics; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D005818:Genetic Engineering; D006801:Humans; D007109:Immunity; D007167:Immunotherapy / Q000379:methods*; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D009504:Neutrophils / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000628:therapy*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D019409:Interleukin-15; D011993:Recombinant Fusion Proteins; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis
BCG; Bladder cancer; Immunotherapy; Interleukin15; Mice