Efficacy of oncolytic reovirus against liver metastasis from pancreatic cancer in immunocompetent models.
Liver metastasis is common in pancreatic cancer patients, and the current treatments are insufficient to improve the clinical outcome. Recently, tumor-targeted replication-competent viruses have been developed as cancer therapy. The aim of this study was to clarify the efficacy of oncolytic reovirus against liver metastases from pancreatic cancer in immunocompetent models. Reovirus serotype 3 and three hamster pancreatic cancer cell lines (HPD1NR, HPD2NR, and HaP-T1) were used in this study. The susceptibility of reovirus to these cell lines was examined. The effect of intraportal administration of reovirus against metastatic liver tumors was evaluated in vivo. Reovirus infected all cell lines and propagated via an activated Ras signalling pathway in vitro. In syngeneic hamster models using the HPD2NR cell line, intraportal administration of reovirus significantly decreased the number and size of treated tumors in comparison with non-treated tumors. Immunohistochemical examination revealed reovirus replication within the tumor cells but not in the surrounding normal tissue and organs. There were no reovirus-related toxicities and deaths. Our results indicate that intraportal administration of reovirus is effective and safe in immunocompetent and syngeneic hamster models of liver metastases from pancreatic cancer, suggesting that reovirus can be developed into an effective therapeutic modality in future.
Himeno
Yoshihisa
Y
Department of Surgery I, Oita University Faculty of Medicine, Oita 879-5593, Japan.
Etoh
Tsuyoshi
T
Matsumoto
Toshifumi
T
Ohta
Masayuki
M
Nishizono
Akira
A
Kitano
Seigo
S
D000818:Animals; D045744:Cell Line, Tumor; D006224:Cricetinae; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D007150:Immunohistochemistry; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy*; D008647:Mesocricetus; D051379:Mice; D041681:NIH 3T3 Cells; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D050504:Oncolytic Viruses / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000628:therapy; D015398:Signal Transduction; D013997:Time Factors; D018631:ras Proteins / Q000378:metabolism
D018631:ras Proteins