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.