title: Potent Antitumor Activity Generated by a Novel Tumor Specific Cytotoxic T Cell.
abstract: Hepatocellular carcinoma is one of the most common malignant neoplasms in the world and is the main cause of death in patients with liver cirrhosis. Surgical intervention is not suitable for majority of hepatocellular carcinoma. Investigation of the effective targeting to the tumor cells is essential for both primary tumors and metastases. Tumor specific cytotoxic T lymphocytes (CTL) have been considered to be the attractive vehicles for delivering therapeutic agents toward various tumor diseases. This study was to explore the distribution pattern of CTL carrying the lentiviral vectors with the characteristic of adenoviral E1 gene under the control of the cell activation-dependent CD40 ligand promoter (Lenti/hCD40L/E1AB). Following transduction with adenoviral vectors containing chimeric type 5 and type 35 fiber proteins (Ad5/35-TRAIL), these CTLs produced infectious virus when exposed to HepG2 cells. We assessed the therapeutic ability of CTLs using MTT, Western blot and colony formation assay. The novel CTL harboring Lenti/hCD40L/E1AB and Ad5/35-TRAIL caused proliferation inhibition and significant apoptosis in hepatocellular carcinoma cell lines. Thus, the novel CTL may be useful for the development of gene therapy approaches to hepatocellular carcinoma.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.forename: Qinhong
authors.initials: Q
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Xuqi
authors.initials: X
authors.lastname: Li
authors.forename: Xufeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Ma
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D015153:Blotting, Western; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000628:therapy; D005434:Flow Cytometry; D015316:Genetic Therapy; D005822:Genetic Vectors; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic
chemical_list: D023201:CD40 Ligand