Local Immune Stimulation by Intravesical Instillation of Baculovirus to Enable Bladder Cancer Therapy
Local Immune Stimulation by Intravesical Instillation of Baculovirus to Enable Bladder Cancer Therapy
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DOI：
10.1038/srep27455
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发表时间：
2016-06-08
影响因子：
4.6
通讯作者：
Wang, Shu
中科院分区：
文献类型：
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作者：
Ang, Wei Xia;Zhao, Ying;Wang, Shu
卡介苗膀胱内灌注目前用于浅表性非肌肉浸润性膀胱癌(NMIBC)的辅助治疗。然而，近40%的NMIBC患者将无法通过卡介苗治疗。为了探讨昆虫杆状病毒载体用于膀胱癌治疗的可行性，我们观察到未转基因的杆状病毒膀胱内注射可上调一组Th1型细胞因子，并提高已建立的原位膀胱癌小鼠的存活率。用杆状病毒载体将CD40配体和IL-15基因共传递到小鼠膀胱内，免疫基因治疗可显著增加小鼠膀胱炎性单核细胞、CD4(+)、CD8(+)和γ-Delta T淋巴细胞的浸润。所有处理的动物都存活了12个月以上，而对照动物在肿瘤接种后大约2个月死亡。我们认为，杆状病毒基因转移载体直接膀胱内注射有可能成为治疗NMIBC的一种新方法。
Intravesical instillation of Bacillus Calmette-Guerin 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-Guerin 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 gamma delta 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.