title: Treatment of multi-focal colorectal carcinoma metastatic to the liver of immune-competent and syngeneic rats by hepatic artery infusion of oncolytic vesicular stomatitis virus.
abstract: Viruses that replicate selectively in cancer cells hold considerable promise as novel therapeutic agents for the treatment of malignancy. We report an orthotopic model of multi-focal colorectal cancer (CRC) metastases in the livers of syngeneic and immune-competent rats, which permitted rigorous testing of oncolytic virus vectors as novel therapeutic agents through hepatic arterial infusion for efficacy and safety. Vesicular stomatitis virus (VSV) is a negative-strand RNA virus with intrinsic oncolytic specificity due to attenuated anti-viral responses in many tumors. After administration at the maximum tolerated dose, the recombinant VSV vector gained access to multi-focal hepatic CRC lesions that led to tumor-selective viral replication and oncolysis. No relevant vector-associated toxicities were noted and in particular, no damage to the hepatic parenchyma was seen. Moreover, the survival rate of vector-treated rats was significantly improved over that of animals in the control treatment group (p = 0.015). Our results demonstrate that hepatic arterial administration of oncolytic VSV is both effective and safe in an immune-competent and syngeneic rat model of multi-focal CRC liver metastasis, suggesting that it can be developed into an effective therapeutic modality in patients in the future.
authors.affiliation: Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Shinozaki
authors.forename: Oliver
authors.initials: O
authors.lastname: Ebert
authors.forename: Savio L C
authors.initials: SL
authors.lastname: Woo
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy*; D005822:Genetic Vectors; D006499:Hepatic Artery / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental; D012367:RNA, Viral / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014721:Vesicular stomatitis Indiana virus / Q000378:metabolism*; D014780:Viruses / Q000378:metabolism*
chemical_list: D012367:RNA, Viral