title: Immunotherapeutic effects of cytokine-induced killer cells combined with CCL21/IL15 armed oncolytic adenovirus in TERT-positive tumor cells.
abstract: The effective antitumor immune responses are dependent on coordinate interaction of various effector cells. Thus, the combination of adoptive immunotherapy and target gene therapy is capable of efficiently generating a productive antitumor immune response. We investigated whether combination of cytokine-induced killer (CIK) cells adoptive immunotherapy and CCL21/IL15 armed oncolytic adenovirus could induce the enhanced antitumor activity. The CCL21/IL15 co-expression oncolytic adenoviruses were constructed by using the AdEasy system, which uses homologous recombination with shuttle plasmids and full length Ad backbones. This conditionally replicating adenoviruses CRAd-CCL21-IL15 could induce apoptosis in TERTp-positive tumor cells for viral propagation, but do not replicate efficiently in normal cells, because the E1A promoter was replaced by telomerase reverse transcriptase promoter (TERTp). Our results showed that the combination of CIK cells and CRAd-CCL21-IL15 could induce higher antitumor activity than either CIK cells or CRAd-CCL21-IL15 alone. This combined treatment could induce the tumor specific cytotoxicity of CTLs (cytotoxic T lymphocytes) in vitro. Moreover, the treatment of established tumors with the combined therapy of CIK cells and CRAd-CCL21-IL15 resulted in tumor regression. This study suggests that the combined treatment by adoptive immunotherapy and gene therapy is a promising strategy for the therapy of tumor.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Department of Hepato-Biliary-Pancreatic Surgery, First Hospital, Jilin University, Changchun 130062, PR China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Ye
authors.affiliation: Ultrasonography department, China-Japan Union Hospital, Jilin University, Changchun 130062, PR China.
authors.forename: Yuan-Qiang
authors.initials: YQ
authors.lastname: Lin
authors.affiliation: The First Hospital of Jilin University, Changchun 130021, PR China.
authors.forename: Xiu-Hua
authors.initials: XH
authors.lastname: Yu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Department of Hepato-Biliary-Pancreatic Surgery, First 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: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Department of Hepato-Biliary-Pancreatic Surgery, First 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; D000818:Animals; D045744:Cell Line, Tumor; D054421:Chemokine CCL21 / Q000235:genetics*; D003131:Combined Modality Therapy; D055612:Cytokine-Induced Killer Cells / Q000502:physiology / Q000637:transplantation*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D019409:Interleukin-15 / Q000235:genetics*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019098:Telomerase / Q000378:metabolism; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D054421:Chemokine CCL21; D019409:Interleukin-15; C509186:TERT protein, human; D019098:Telomerase
keywords: CCL21; CIK cells; Combination therapy; IL15; Oncolytic adenoviruses