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Updated: Jul 6, 2026
Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus
Published on: May 13, 2021
Sensitivity of squamous cell carcinoma lymph node metastases to herpes oncolytic therapy
Zhenkun Yu1, Sen Li, Yu-Yao Huang
1Head and Neck Service and Gastric, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Purpose:
Cancer metastases may have phenotypic and genetic differences from their primary cancers of origin. Engineered, replication-competent, attenuated viruses based on herpes simplex virus-1 (HSV-1) have shown potent oncolytic effects in treating primary tumors in animal tumor models, but their efficacy in treating lymph node metastases is poorly understood. We compared the efficacy of an attenuated oncolytic HSV-1 (NV1023) in treating a series of murine squamous carcinoma cell lines derived from serial implantation and harvest from metastatic lymph nodes.
Experimental Design And Results:
The auricles of C3H/HeJ mice were implanted with SCCVII. Cervical nodal metastases were isolated, expanded in vitro, and reimplanted into new mice. A series of cell lines (LN1-LN7) were generated through seven serial passages. Cells from higher LN passages showed consistent trends toward increased migratory and invasive ability, increased cell surface nectin-1 (an HSV-1 receptor) expression, and increased glycoprotein D binding. Exposure to NV1023 showed increased viral entry, replication, and cytotoxicity with higher LN passages. Intratumoral injection of NV1023 in a murine flank tumor model caused significantly greater tumor regression and increased viral infection of LN7 compared with SCCVII.
Conclusions:
These results show that lymph node metastases may undergo selection for characteristics, including increased nectin-1 expression, that make them more sensitive targets for herpes oncolytic therapy. These findings support the clinical application of these agents for the treatment of lymph node metastases.
Insights
Lymph node metastases become more sensitive to herpes oncolytic therapy with increased nectin-1 expression. This suggests engineered herpes simplex virus-1 (HSV-1) is effective for treating lymph node metastases.
Area of Science:
- Oncolytic virology
- Cancer metastasis research
- Immunotherapy
Background:
- Cancer metastases can differ genetically and phenotypically from primary tumors.
- Engineered herpes simplex virus-1 (HSV-1) shows promise for treating primary tumors but its efficacy against lymph node metastases is unclear.
Purpose of the Study:
- To evaluate the efficacy of an attenuated oncolytic HSV-1 (NV1023) against murine squamous carcinoma cell lines derived from lymph node metastases.
- To investigate phenotypic and genetic changes in lymph node metastases that may impact oncolytic virus therapy.
Main Methods:
- Generated serial cell lines (LN1-LN7) from metastatic lymph nodes of mice.
- Assessed migratory and invasive abilities, and nectin-1 (HSV-1 receptor) expression in cell lines.
- Compared NV1023 entry, replication, and cytotoxicity in cell lines with varying passage numbers.
- Evaluated NV1023 efficacy in a murine flank tumor model with lymph node metastases.
Main Results:
- Higher passage lymph node cell lines exhibited increased migration, invasion, and nectin-1 expression.
- NV1023 demonstrated enhanced viral entry, replication, and cytotoxicity in higher passage cells.
- Intratumoral NV1023 treatment resulted in significant tumor regression and increased viral infection in lymph node metastases compared to primary tumor cells.
Conclusions:
- Lymph node metastases can acquire characteristics, such as increased nectin-1 expression, making them more susceptible to oncolytic herpes virus therapy.
- These findings support the clinical use of oncolytic HSV-1 for treating lymph node metastases.
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