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Updated: Sep 9, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Selective Activation of Conditionally Replicating Influenza A Virus in Pulmonary Tumors for Enhanced Oncolytic
Ji Chen1,2, Xiya Guo1, Yanqiao Ma3
1School of Pharmacy, Qingdao University, Qingdao, 266021, China.
Abstract:
Influenza A virus demonstrates significant potential as an oncolytic agent. Nevertheless, being replication-competent pathogens, they may induce adverse effects in cancer patients who have compromised immune systems. Here, the results show that the 4-hydroxytamoxifen (4-HT)-dependent H1N1 influenza virus S218 can inhibit the proliferation and lung metastasis of melanoma in vivo, and 4-HT enhances the anti-tumor effect of S218 virus. To activate the S218 virus in the tumors, tumor-targeted nanostructured lipid carriers (NLCs) modified with folate (FA) are developed to encapsulate 4-HT. This approach improves the tumor-targeting capability and anti-tumor immunity of the S218 virus. Furthermore, the combination of the S218 virus with the small molecule STING agonist SR717 further enhances the regression of lung metastases. The findings demonstrate a novel oncolytic strategy utilizing nanocarriers to deliver small-molecule drugs for activating viruses in the tumors, offering insights for oncolytic virus development.
Insights
This study shows that a modified influenza A virus (S218) effectively inhibits melanoma growth and metastasis. Nanoparticle delivery of 4-hydroxytamoxifen (4-HT) enhances its anti-tumor effects, offering a promising oncolytic virus therapy.
Area of Science:
- Oncology
- Virology
- Nanotechnology
Background:
- Influenza A virus shows potential as an oncolytic agent.
- Replication-competent influenza viruses may cause adverse effects in immunocompromised cancer patients.
Purpose of the Study:
- To develop a novel oncolytic strategy using a 4-hydroxytamoxifen (4-HT)-dependent H1N1 influenza virus (S218) to inhibit melanoma.
- To enhance the anti-tumor efficacy and safety of the S218 virus through targeted delivery and combination therapy.
Main Methods:
- Developed folate (FA)-modified nanostructured lipid carriers (NLCs) to encapsulate 4-HT for tumor-targeted delivery.
- Administered the S218 virus and 4-HT-loaded NLCs in vivo to evaluate anti-tumor effects on melanoma.
- Investigated the combination therapy of S218 virus, 4-HT-loaded NLCs, and a STING agonist (SR717).
Main Results:
- The 4-HT-dependent S218 virus inhibited melanoma proliferation and lung metastasis in vivo.
- 4-HT significantly enhanced the anti-tumor effect of the S218 virus.
- FA-modified NLCs improved tumor targeting and anti-tumor immunity.
- Combination therapy with S218 virus, 4-HT-loaded NLCs, and SR717 further enhanced lung metastasis regression.
Conclusions:
- A novel oncolytic strategy was developed using nanocarriers for targeted delivery of small-molecule drugs to activate oncolytic viruses within tumors.
- This approach enhances the efficacy and safety of oncolytic influenza virus therapy for melanoma.
- The findings provide valuable insights for the development of advanced oncolytic virus-based cancer treatments.
