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Updated: Dec 27, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Folate-conjugated herpes simplex virus for retargeting to tumor cells
Zhi-Qiang Ye1, Chang-Lin Zou2, Han-Bin Chen2
1Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China.
Background:
Herpes simplex virus type 1 (HSV-1)-mediated oncolytic therapy is a promising cancer treatment modality. However, viral tropism is considered to be one of the major stumbling blocks to the development of HSV-1 as an anticancer agent.
Methods:
The surface of oncolytic HSV-1 G207 was covalently modified with folate-poly (ethylene glycol) conjugate (FA-PEG). The specificities and tumor targeting efficiencies of modified or unmodified G207 particles were analyzed by a real-time polymerase chain reaction at the level of cell attachment and entry. Immune responses were assessed by an interleukin-6 release assay from RAW264.7 macrophages. Biodistribution and in vivo antitumoral activity after intravenous delivery was evaluated in BALB/c nude mice bearing subcutaneous KB xenograft tumors.
Results:
FA-PEG-HSV exhibited enhanced targeting specificity for folate receptor over-expressing tumor cells and had lower immunogenicity than the unmodified HSV. In vivo, the FA-PEG-HSV group revealed an increased anti-tumor efficiency and tumor targeting specificity compared to the naked HSV.
Conclusions:
These results indicate that folate-conjugated HSV G207 presents a folate receptor-targeted oncolytic virus with a potential therapeutic value via retargeting to tumor cells.
Insights
Folate-conjugated oncolytic Herpes simplex virus type 1 (HSV-1) shows improved tumor targeting and reduced immunogenicity. This enhanced HSV-1 G207 demonstrates greater anti-tumor efficacy, offering potential for cancer therapy.
Area of Science:
- Oncolytic virotherapy
- Cancer treatment
- Molecular targeting
Background:
- Herpes simplex virus type 1 (HSV-1) oncolytic therapy shows promise for cancer treatment.
- Viral tropism remains a significant challenge for HSV-1 anticancer applications.
Purpose of the Study:
- To enhance the tumor-targeting specificity of oncolytic HSV-1 G207.
- To evaluate the therapeutic potential of folate-conjugated HSV-1.
Main Methods:
- Covalent modification of HSV-1 G207 with folate-poly(ethylene glycol) conjugate (FA-PEG).
- Assessment of cell attachment, entry, and tumor targeting efficiency using real-time PCR.
- Evaluation of immunogenicity via interleukin-6 release assay.
- In vivo biodistribution and antitumor activity assessment in mice.
Main Results:
- FA-PEG-HSV demonstrated enhanced targeting specificity for folate receptor-overexpressing tumor cells.
- Modified HSV exhibited lower immunogenicity compared to unmodified HSV.
- In vivo studies showed increased antitumor efficiency and tumor targeting specificity for FA-PEG-HSV.
Conclusions:
- Folate-conjugated HSV G207 acts as a targeted oncolytic virus.
- Retargeting HSV-1 to tumor cells via folate conjugation holds therapeutic potential.
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