Yan Yang, Li Songyan, Jia Tingting, Du Xiaohui, Xu Yingxin, Zhao Yunshan, Li Li, Liang Kai, Liang Wentao, Sun Huiwei, Li Rong
General Surgery Department, Chinese PLA General Hospital, 28 Fuxing Road, Haidian, Beijing, 100853, People's Republic of China.
Tumour Biol. 2015 Jun;36(6):4535-43. doi: 10.1007/s13277-015-3098-7. Epub 2015 Jan 28.
Addition of immunoregulation factor to an oncolytic adenovirus being constructed is a developmental step in tumor gene therapy; however, cytokine IL-15 has not been frequently used as a potential cancer therapy agent. Here, we constructed an E2F-1 promoter oncolytic adenovirus based on type 5 adenovirus, which induces viral replication and proliferation in targeted tumor cells. We inserted the IL-15 gene into the E3 region of the model and found that human IL-15 expressing oncolytic adenovirus (Ad-E2F/IL15) shows a more intense antitumor effect than simple oncolytic viruses (Ad-E2F) do. Precisely because IL-15 can activate natural killer (NK) cells, CD8(+)T cells, and other immune cells, in antitumor therapy, Ad-E2F/IL15 was used in combination with cytotoxic T lymphocytes (CTL) to create a virus that can induce IL-15 gene expression while lysing tumors and stimulating the activity and function of adoptive immune cells. The therapeutic effect of this therapy is clearly stronger than that of a single application of oncolytic viruses or CTL, and hence, it could be a potential new tumor therapy.
在构建溶瘤腺病毒中添加免疫调节因子是肿瘤基因治疗的一个发展步骤；然而，细胞因子IL-15尚未经常被用作潜在的癌症治疗药物。在此，我们基于5型腺病毒构建了一种E2F-1启动子溶瘤腺病毒，其可诱导靶向肿瘤细胞中的病毒复制和增殖。我们将IL-15基因插入该模型的E3区域，发现表达人IL-15的溶瘤腺病毒（Ad-E2F/IL15）比单纯的溶瘤病毒（Ad-E2F）显示出更强的抗肿瘤作用。正是因为IL-15可激活自然杀伤（NK）细胞、CD8(+)T细胞和其他免疫细胞，在抗肿瘤治疗中，Ad-E2F/IL15与细胞毒性T淋巴细胞（CTL）联合使用，以创建一种在裂解肿瘤并刺激过继免疫细胞的活性和功能的同时可诱导IL-15基因表达的病毒。这种治疗方法的治疗效果明显强于单独应用溶瘤病毒或CTL，因此，它可能是一种潜在的新型肿瘤治疗方法。
