title: Pancreatic carcinoma-specific immunotherapy using novel tumor specific cytotoxic T cells.
abstract: Pancreatic cancer represents one of the most lethal human cancers. Investigation of the effective targeting to the tumor cells is essential for both primary tumors and metastases. Tumor specific cytotoxic T lymphocytes (CTLs) have recently 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 particles containing chimeric type 5 and type 35 fiber proteins (Ad5/35-TRAIL), these CTLs produced infectious virus when exposed to SW1990 cells. We found that the novel CTL harboring Lenti/hCD40L/E1AB and Ad5/35-TRAIL inhibited pancreatic cancer cell growth and angiogenesis in vitro and in vivo. Furthermore, Ad5/35-TRAIL transduced CTL induced significant apoptosis in pancreatic carcinoma cell lines and upregulated IFN-gamma (IFN-γ) secretion of CTLs. Importantly, Ad5/35-TRAIL transduced CTLs had no inhibitory effect on normal cells. Thus, the novel CTLs may be safe and feasible for the development of gene therapy approaches to pancreatic carcinoma.
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zong
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Wanxing
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Qinhong
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Lun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017498:Adenovirus E1 Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D023201:CD40 Ligand / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016086:Lentivirus / Q000235:genetics; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011401:Promoter Regions, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D017498:Adenovirus E1 Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D023201:CD40 Ligand
keywords: immunotherapy; pancreatic carcinoma; tumor specific cytotoxic T lymphocytes