Ang Wei Xia, Zhao Ying, Kwang Timothy, Wu Chunxiao, Chen Can, Toh Han Chong, Mahendran Ratha, Esuvaranathan Kesavan, Wang Shu
Department of Biological Sciences, National University of Singapore, 117543 Singapore.
Institute of Bioengineering and Nanotechnology, 138669 Singapore.
Sci Rep. 2016 Jun 8;6:27455. doi: 10.1038/srep27455.
Intravesical instillation of Bacillus Calmette-Guérin is currently used as adjuvant therapy for superficial, non-muscle invasive bladder cancer (NMIBC). However, nearly 40% of patients with NMIBC will fail Bacillus Calmette-Guérin therapy. In an attempt to investigate the feasibility of using insect baculovirus-based vectors for bladder cancer therapy, we observed that intravesical instillation of baculoviruses without transgene up-regulated a set of Th1-type of cytokines and increased the survival rate of mice bearing established orthotopic bladder tumors. When baculoviral vectors were used to co-deliver the mouse CD40 ligand and IL-15 genes through intravesical instillation, the immunogene therapy triggered significantly increased bladder infiltrations of inflammatory monocytes, CD4(+), CD8(+) and γδ T lymphocytes. All treated animals survived beyond 12 months whereas control animals died around 2 months after tumor inoculation. We conclude that direct intravesical instillation of baculoviral gene transfer vectors holds the potential to be a novel therapeutic modality for NMIBC.
膀胱内灌注卡介苗目前用作浅表性非肌肉浸润性膀胱癌（NMIBC）的辅助治疗。然而，近40%的NMIBC患者卡介苗治疗会失败。为了研究使用基于昆虫杆状病毒的载体进行膀胱癌治疗的可行性，我们观察到无转基因的杆状病毒膀胱内灌注上调了一组Th1型细胞因子，并提高了已建立原位膀胱肿瘤小鼠的存活率。当通过膀胱内灌注使用杆状病毒载体共递送小鼠CD40配体和IL-15基因时，免疫基因治疗引发炎症单核细胞、CD4(+)、CD8(+)和γδ T淋巴细胞向膀胱的浸润显著增加。所有接受治疗的动物存活超过12个月，而对照动物在肿瘤接种后约2个月死亡。我们得出结论，杆状病毒基因转移载体的直接膀胱内灌注有可能成为NMIBC的一种新型治疗方式。
