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Int Immunopharmacol. 2015 Sep;28(1):487-93. doi: 10.1016/j.intimp.2015.07.005. Epub 2015 Jul 24.

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

Author information

1
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, China-Japan Union Hospital, Jilin University, Changchun 130062, PR China.
2
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, PR China.
3
Second Hospital of Jilin University, Changchun, Jilin Province 130021, PR China.
4
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, China-Japan Union Hospital, Jilin University, Changchun 130062, PR China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China.
5
Fourth Hospital of Jilin University, Changchun 130062, PR China.
6
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, China-Japan Union Hospital, Jilin University, Changchun 130062, PR China. Electronic address: myth0317@yeah.net.

Abstract

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-CCL20-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.

KEYWORDS:

CCL20; CD40L; cancer immunotherapy; oncolytic adenovirus; transgene

PMID:
26208317
DOI:
10.1016/j.intimp.2015.07.005
[Indexed for MEDLINE]

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