title: Enhanced growth suppression of TERT-positive tumor cells by oncolytic adenovirus armed with CCL20 and CD40L.
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.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, China-Japan Union Hospital, Jilin University, Changchun 130062, PR China.
authors.forename: Guang-Yao
authors.initials: GY
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, PR China.
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, China-Japan Union Hospital, Jilin University, Changchun 130062, PR China.
authors.forename: Qing-Lin
authors.initials: QL
authors.lastname: Li
authors.affiliation: Second Hospital of Jilin University, Changchun, Jilin Province 130021, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Second Hospital of Jilin University, Changchun, Jilin Province 130021, PR China.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Zhu
authors.affiliation: Second Hospital of Jilin University, Changchun, Jilin Province 130021, PR China.
authors.forename: Yue-Hui
authors.initials: YH
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Liu
authors.affiliation: Fourth Hospital of Jilin University, Changchun 130062, PR China.
authors.forename: Ya-Gang
authors.initials: YG
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D023201:CD40 Ligand / Q000235:genetics*; D045744:Cell Line, Tumor; D054418:Chemokine CCL20 / Q000235:genetics*; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000628:therapy; D050504:Oncolytic Viruses / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019098:Telomerase / Q000235:genetics*
chemical_list: C108355:CCL20 protein, human; D054418:Chemokine CCL20; D023201:CD40 Ligand; D019098:Telomerase
keywords: CCL20; CD40L; cancer immunotherapy; oncolytic adenovirus; transgene