Antitumor activity of recombinant Bacille Calmette-Guerin secreting interleukin-15-Ag85B fusion protein against bladder cancer

作者：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

来源：International Immunopharmacology, 2016, 35: 327-331.

DOI：10.1016/j.intimp.2016.03.007

• BCG
• Bladder cancer
• Interleukin15
• Immunotherapy
• Mice

Mycobacterium bovis Bacillus Calmette-Guerin (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 gamma delta 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-1 alpha) 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.

• 出版日期2016-6