Erschienen in:
01.06.2015 | Research Article
Combined therapy with CTL cells and oncolytic adenovirus expressing IL-15-induced enhanced antitumor activity
verfasst von:
Yang Yan, Songyan Li, Tingting Jia, Xiaohui Du, Yingxin Xu, Yunshan Zhao, Li Li, Kai Liang, Wentao Liang, Huiwei Sun, Rong Li
Erschienen in:
Tumor Biology
|
Ausgabe 6/2015
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Abstract
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.