Enhanced growth suppression of TERT-positive tumor cells by oncolytic adenovirus armed with CCL20 and CD40L

文献类型： 外文期刊

第一作者： Liu, Guang-yao

作者： Liu, Guang-yao;Li, Qing-lin;Liu, Ming-yuan;Li, Yang;Li, Zhi-jie;Jin, Yan;Zhu, Yu-hui;Wang, Yue-hui;Li, Ya-gang;Liu, Ming-yuan

作者机构：

关键词： CCL20;CD40L;oncolytic adenovirus;transgene;cancer immunotherapy

期刊名称：INTERNATIONAL IMMUNOPHARMACOLOGY （ 影响因子：4.932； 五年影响因子：4.624 ）

ISSN： 1567-5769

年卷期： 2015 年 28 卷 1 期

页码：

收录情况： SCI

摘要： Conditionally replicating adenoviruses (CRAds) selectively replicate in cancer cells and induce cell lysis, which represents a potential platform for cancer immunotherapy. The chemokine CCL20 exerts antitumor activity via chemoattraction of immature dendritic cells (DCs) and lymphocytes. However, the activation and maturation status of DCs is a limiting factor in the DCs-based immunity response. CD40L induces the phenotypic maturation of DCs, mediates DCs cytokine secretion, and increases the expression of FasL, which mediates apoptosis. We constructed a CCL20/CD40L co-expression CRAds (Ad-CCL2O-CD40L) based on the AdEasy system. Ad-CCL20-CD40L was constructed from three plasmids, pGTE-CD40L, pShuttle-CMV-CCL20 and AdEasy-1, and was homologously recombined and propagated in the Escherichia coli strain BJ5183 and the packaging cell line HEK-293, respectively. Ad-CCL20-CD40L selectively replicates in TERT-positive tumor cells because the pGTE-CD40L plasmid contains the telomerase reverse transcriptase promoter (TERTp). Our results showed that Ad-CCL20-CD40L induced oncolytic effects and tumor-specific cytotoxicity of cytotoxic T lymphocytes (CTLs) in vitro. This study suggests that Ad-CCL20-CD40L can induce the antitumor immune response and that this platform can be modified to generate novel CRAds with other transgenes. (C) 2015 Elsevier B.V. All rights reserved.

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