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Antitumor activity of recombinant Bacille Calmette-Guérin secreting interleukin-15-Ag85B fusion protein against bladder cancer.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2016 Jun; Vol. 35, pp. 327-331. Date of Electronic Publication: 2016 Apr 16. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Acyltransferases genetics
Animals
Antigens, Bacterial genetics
Bacterial Proteins genetics
Cell Movement drug effects
Female
Genetic Engineering
Humans
Immunity
Interleukin-15 genetics
Lymphocyte Depletion
Mice
Mice, Inbred C57BL
Mycobacterium bovis genetics
Recombinant Fusion Proteins genetics
Urinary Bladder Neoplasms immunology
Immunotherapy methods
Interleukin-15 metabolism
Mycobacterium bovis immunology
Neutrophils physiology
Recombinant Fusion Proteins therapeutic use
Urinary Bladder Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 35
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 27093372
- Full Text :
- https://doi.org/10.1016/j.intimp.2016.03.007