Oncolysis of hepatic metastasis of colorectal cancer by recombinant vesicular stomatitis virus in immune-competent mice.
With currently available treatments, patients with metastatic colorectal cancer (CRC) have a median survival of 14.8 months and a 5-year survival rate of less than 10%. In recent years, tumor-targeted replicating viruses have rapidly emerged as potential novel oncolytic agents for cancer treatment. Vesicular stomatitis virus (VSV) is a negative-strand RNA virus with inherent selectivity for replication in tumor cells due to their attenuated antiviral response. VSV is particularly appealing as an oncolytic agent for its exceptionally rapid replication cycle in tumor cells, whereby it is capable of manifesting its maximal oncolytic effects before the onset of neutralizing antiviral immune responses in the host. In this study, we used a recombinant VSV vector expressing the green fluorescent protein gene (rVSV-GFP) to monitor VSV replication easily in CRC cells. Using this GFP-expressing virus, we found that rVSV-GFP efficiently replicated and lysed murine and human CRC cell lines in vitro. We also evaluated the potential of rVSV-GFP to treat MCA26 CRC metastases implanted orthotopically into the livers of syngeneic BALB/c mice. We provide conclusive evidence that rVSV-GFP is able to replicate extensively in the tumors, but not in normal liver cells, in tumor-bearing mice. A single intratumoral injection also caused extensive tumor necrosis, which led to a significant prolongation of animal survival. Our results indicate that VSV can be an effective and safe oncolytic agent against hepatic CRC metastasis in immune-competent mice and may be developed for the treatment of cancer patients in the future.
Huang
Tian-Gui
TG
Carl C. Icahn Center for Gene Therapy and Molecular Medicine, New York, New York 10029-6574, USA.
Ebert
Oliver
O
Shinozaki
Katsunori
K
García-Sastre
Adolfo
A
Woo
Savio L C
SL
D000818:Animals; D015179:Colorectal Neoplasms / Q000556:secondary*; D017930:Genes, Reporter; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D051379:Mice; D009362:Neoplasm Metastasis / Q000473:pathology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics* / Q000378:metabolism
D011993:Recombinant Fusion Proteins