Considerations for intravascular administration of oncolytic herpes virus for the treatment of multiple liver metastases
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Updated: Jul 4, 2026
Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats
Published on: April 15, 2016
Naohiro Nomura1, Hideki Kasuya, Izuru Watanabe
1Department of Surgery II, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. sjypy948@yahoo.co.jp
Purpose:
Oncolytic viral therapy is a newly developed modality for treating tumors. Many clinical trials using oncolytic virus have been performed worldwide, but most of them have used local injection in the tumor. Determination of the effect and safety of intravascular virus injection instead of local injection is necessary for clinical use against multiple liver metastases and systemic metastases.
Methods:
To evaluate the efficacy and safety of intravascular virus therapy, mice bearing multiple liver metastases were treated by intraportal or intravenous administration of the herpes simplex virus type 1 (HSV-1) mutant, hrR3. Mice treated with hrR3 were killed and organs were harvested for lacZ staining and PCR analysis. Inactivation of oncolytic virus in bloodstream was assessed by neutralization assay in vitro. Infectious activity of hrR3 with vascular endothelial cells was evaluated by replication and cytotoxicity assay.
Results:
The survival rate of animals treated by hrR3 was significantly improved compared with the untreated group. lacZ staining and PCR analysis demonstrated detectable virus in the tumor but not in normal tissue or other organs except for the adrenal glands. We also showed that vascular endothelial cells allowed virus replication, while normal hepatocytes did not, and human anti-HSV antibody revealed attenuation of the infectious activity of hrR3.
Conclusions:
Intravascular delivery of hrR3 is effective in treating multiple liver metastases, however, several points must be kept in mind at the time of human clinical trials using intravascular virus administration in order to avoid critical side effects.
Insights
Intravascular administration of herpes simplex virus type 1 (HSV-1) mutant hrR3 improved survival in mice with liver metastases. The oncolytic virus targeted tumors effectively, with minimal spread to healthy tissues, showing promise for systemic cancer treatment.
Area of Science:
- Oncolytic virology
- Cancer therapy
- Viral vector delivery
Background:
- Oncolytic viral therapy is an emerging cancer treatment.
- Current clinical trials primarily use local tumor injection.
- Intravascular delivery requires evaluation for treating widespread metastases.
Purpose of the Study:
- To assess the efficacy and safety of intravascular administration of an oncolytic virus.
- To determine the potential of intraportal or intravenous delivery for liver metastases.
- To compare intravascular delivery with traditional local injection methods.
Main Methods:
- Mice with liver metastases received intraportal or intravenous administration of herpes simplex virus type 1 (HSV-1) mutant hrR3.
- Organ analysis included lacZ staining and PCR for virus detection.
- In vitro assays assessed virus inactivation in blood and replication in endothelial cells.
Main Results:
- Intravascular hrR3 treatment significantly improved animal survival rates.
- Virus was detected in tumors but not in most normal tissues, indicating tumor specificity.
- Vascular endothelial cells supported virus replication, while hepatocytes did not.
Conclusions:
- Intravascular delivery of hrR3 demonstrates efficacy against multiple liver metastases.
- Consideration of potential side effects is crucial for human clinical trials.
- Further research is needed to optimize intravascular oncolytic virotherapy.
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