New pancreatic carcinoma model for studying oncolytic adenoviruses in the permissive Syrian hamster.
Syrian hamster is a practical animal model for studying the systemic effects of oncolytic vectors derived from adenovirus serotype 5 (Ad5). Ad5 replicates well in Syrian hamster tissues, and Syrian hamster cell lines are available that are known to support Ad5 replication. In this study, we established four new Syrian hamster cell lines from transplantable pancreatic, renal, hepatic and lung tumors. The pancreatic cell line (SHPC6) and the renal cell line were highly permissive for Ad5 replication. The SHPC6 cell line formed disseminated intraperitoneal tumors when cells were injected into the peritoneal cavity. INGN 007, an oncolytic Ad5-based vector, completely reversed the growth of disseminated intraperitoneal SHPC6 tumor nodules following intraperitoneal injection of the vector, leading to 100% survival of the treated animals. SHPC6 cells also formed subcutaneous tumors, whose growth was suppressed by INGN 007 following intratumoral injection. INGN 007 replicated in both the intraperitoneal and subcutaneous SHPC6 tumors. Following intraperitoneal injection, INGN 007 did not replicate in the livers of hamsters with intraperitoneal SHPC6 tumors, and was not hepatotoxic. These studies suggest that the SHPC6 cell line may be useful as a model for disseminated pancreatic cancer, and that INGN 007 may be a safe and effective vector to treat these tumors.
Spencer
J F
JF
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, MO 63104, USA.
Sagartz
J E
JE
Wold
W S M
WS
Toth
K
K
D000256:Adenoviridae / Q000502:physiology; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D045744:Cell Line, Tumor; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008647:Mesocricetus; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D023041:Xenograft Model Antitumor Assays