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.
Highlights
Accompany with a 5-year overall survival rate less than 7%, pancreatic cancer is the fourth leading cause of cancer related deaths in the United States [1]
We first used a CD40 ligand (CD40L)/E1 lentivirus that carrying the adenovirus E1 gene to transduce the cytotoxic T lymphocytes (CTLs) (CD40L/E1CTL), the schema was described in methods, and western blot was used to detect the suitable MOIs of CD40L/ E1-CTL
CTLs were infected with the different CD40L/ E1 MOIs for 48 h, and the E1 adenovirus protein expression was analyzed by western blot (Figure 1)
Summary
Accompany with a 5-year overall survival rate less than 7%, pancreatic cancer is the fourth leading cause of cancer related deaths in the United States [1]. The only curative treatment for pancreatic cancer is pancreaticoduodenectomy. Gemcitabine is the most effective chemotherapy drug for advanced pancreatic cancer, improving survival rate as compared with 5-fluorouracil (5-FU) [2, 3]. Recent trials showed that gemcitabine failed to increase survival when combined with other chemotherapeutic drugs [2, 4]. It is urgent needed to find a new therapy for advanced pancreatic cancer. Cancer cells including pancreatic cancer cells could be recongnized by CTLs [5, 6]. Tumor infiltrated with CTLs and T helper cells is a favourable prognostic factor for pancreatic cancer [7]. Tumor-reactive T cells, isolated from blood of cancer patients, are capable of tumor rejection [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
