Masaki Nagasato1,2, Yosei Rin1,2, Yuki Yamamoto1,2, Marina Henmi1,2, Nobuyoshi Hiraoka3, Fumiko Chiwaki4, Keisuke Matsusaki5, Masatoshi Tagawa6, Hiroki Sasaki4, Kazunori Aoki7. 1. Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan. 2. NCC Cancer Science, Tokyo Medical and Dental University, Tokyo, Japan. 3. Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan. 4. Department of Translational Oncology, National Cancer Center Research Institute, Tokyo, Japan. 5. Kaname Second Clinic, Kanamecho Hospital, Tokyo, Japan. 6. Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan. 7. Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan kaoki@ncc.go.jp.
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 surgically-resected 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 PFW-displaying vector increased efficiency in two out of four cases. For ascites samples, both vectors increased gene-transduction 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. Copyright
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 surgically-resected 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 PFW-displaying vector increased efficiency in two out of four cases. For ascites samples, both vectors increased gene-transduction 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. Copyright