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Updated: Jun 29, 2025
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Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus
Published on: May 13, 2021
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Decrease in Heparan Sulphate Binding in Tropism-Retargeted Oncolytic Herpes Simplex Virus (ReHV) Delays Blood
Andrea Vannini1,2, Federico Parenti1, Cristina Forghieri1
1Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy.
Cancers
|March 28, 2024
Summary
Modifying herpes simplex virus (HSV) glycoprotein C to reduce binding to glycosaminoglycans (GAGs) prolonged its circulation time. This enhanced HSV
Area of Science:
- Oncolytic virotherapy
- Viral immunology
- Molecular virology
Background:
- Cell-surface glycosaminoglycans (GAGs) play a role in herpes simplex virus (HSV) infection.
- The interaction of HSV with GAGs affects its in vivo behavior and therapeutic potential.
Purpose of the Study:
- To enhance the anticancer efficacy of systemically administered retargeted oncolytic HSV (ReHV).
- To decrease ReHV binding to GAGs on endothelial cells, blood cells, and off-tumor tissues.
Main Methods:
- Deletion of seven amino acids from glycoprotein C (gC) of R-337 ReHV, critical for GAG interaction, creating R-399 ReHV.
- Evaluation of R-399's half-life, biodistribution, and anticancer efficacy in vivo.
Main Results:
- R-399 exhibited a prolonged half-life in circulation compared to the parent ReHV.
- Enhanced biodistribution of R-399 to tumor-positive lungs and tumor-negative liver.
- Significantly increased efficacy against lung metastases with intravenous (IV) administration, but not subcutaneous tumors with intratumoral (IT) administration.
Conclusions:
- Partial impairment of gC-GAG interaction prolongs ReHV circulation time.
- Increased ReHV uptake by tissues and tumors enhances systemic anticancer efficacy.
- This strategy offers a promising approach for improving oncolytic virotherapy effectiveness.
