A tumor-targeting adenovirus with high gene-transduction efficiency for primary pancreatic cancer and ascites cells

Abstract

Background: Optimizing targeting strategies for vectors in order to enhance antitumor activity and secure patient safety is important for cancer gene therapy. We previously identified two pancreatic cancer-targeting ligands (PFWSGAV: PFW and SYENFSA: SYE) by screening an adenovirus library in vivo and in vitro, respectively. Materials and Methods: To examine clinical usefulness, we assessed gene-transduction efficiency using surgicallyresected pancreatic cancer specimens and ascites cellS. Results: For surgical specimens, vectors displaying PFW and SYE improved transduction efficiency by 4.4-and 4.3-fold, respectively. The SYE-displaying vector was >2-fold more efficient for all seven cases, whereas the PFWdisplaying vector increased efficiency in two out of four caseS. For ascites samples, both vectors increased genetransduction efficiency of epithelial cell adhesion molecule (EpCAM)-positive ascites cells by >2-fold in two out of five caseS. Conclusion: Both vectors enhanced adenovirus infectivity of pancreatic cancer cells and have potential for gene therapy of pancreatic cancer; therefore they should be further evaluated in clinical studieS.