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
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Int Immunopharmacol. 2016 Jun;35:327-331. doi: 10.1016/j.intimp.2016.03.007. Epub 2016 Apr 16.
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.
牛分枝杆菌卡介苗（BCG）用于治疗膀胱癌。BCG灌注后中性粒细胞向膀胱募集对膀胱肿瘤发挥抗肿瘤活性。我们最近证明，γδT细胞产生的白细胞介素（IL）-17A在BCG灌注后中性粒细胞向膀胱募集中起作用。已知IL-15在炎症期间中性粒细胞迁移中起重要作用。我们之前构建了一种表达IL-15与Ag85B融合蛋白的重组BCG菌株（BCG-IL-15）用于预防结核分枝杆菌感染。在此我们比较了BCG-IL-15与重组BCG-Ag85B（BCG）在预防膀胱癌方面的疗效。六周龄雌性C57BL/6小鼠在膀胱内接种MB49膀胱肿瘤细胞，随后膀胱内接种BCG或BCG-IL-15。与BCG治疗相比，BCG-IL-15治疗显著延长了接种膀胱癌细胞小鼠的生存期。BCG-IL-15治疗的小鼠中性粒细胞浸润显著增加，同时膀胱内趋化因子（MIP-2和MIP-1α）增加。因此，BCG-IL-15对膀胱中性粒细胞浸润发挥了累加效应。BCG-IL-15可能是一种有前景的非肌层浸润性膀胱癌治疗药物。
