Pancreatic carcinoma-specific immunotherapy using novel tumor specific cytotoxic T cells
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Jianjun Lei1,*, Zheng Wu1,*, Zhengdong Jiang1, Jiahui Li1, Liang Zong1, Xin Chen1, Wanxing Duan1, Qinhong Xu1, Lun Zhang1, Liang Han1, Qingyong Ma1, Zheng Wang1, Dong Zhang1
1Department of Hepatobiliary and Pancreas Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi’an 710061, Shaanxi Province, China
*These authors contributed equally to this work
Zheng Wang, email: [email protected]
Dong Zhang, email: [email protected]
Keywords: tumor specific cytotoxic T lymphocytes, immunotherapy, pancreatic carcinoma
Received: January 24, 2016 Accepted: September 24, 2016 Published: November 19, 2016
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.
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