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.

journal_name

Int J Cancer

authors

Shinozaki K,Ebert O,Woo SL

doi

10.1002/ijc.20772

keywords:

subject

Has Abstract

pub_date

2005-04-20 00:00:00

pages

659-64

issue

4

eissn

0020-7136

issn

1097-0215

journal_volume

114

pub_type

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