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Updated: Jul 9, 2026

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Combined VSV oncolytic virus and chemotherapy for squamous cell carcinoma
Chih-Kwang Sung1, Bryan Choi, Georges Wanna
1Department of Otolaryngology-Head and Neck Surgery, Mount Sinai School of Medicine, New York, New York 10029, USA.
Objectives:
Vesicular stomatitis virus (VSV) is a negative-strand ribonucleic acid (RNA) virus that replicates specifically in tumor cells and has oncolytic effects in a variety of malignant tumors. We previously demonstrated recombinant VSV vectors incorporating viral fusion protein (rVSV-F) and interleukin 12 (rVSV-IL12) to have significant antitumor effects against squamous cell carcinoma (SCC) in a murine model. Here we evaluate the potential to combine a potent chemotherapeutic agent for SCC (cisplatin) with rVSV-F and rVSV-IL12 to improve efficacy.
Study Design:
In vitro, three SCC cell lines were tested using rVSV-F and rVSV-IL12 with cisplatin, monitoring viral replication and cell survival. In an orthotopic floor of mouth murine SCC model, intratumoral injections of virus combined with systemic cisplatin were tested for tumor control and animal survival.
Results:
In vitro, virus and cisplatin combination demonstrated rapid replication and enhanced tumor cell kill. Human keratinocytes were unaffected by virus and cisplatin. In vivo, combined rVSV-F with cisplatin reduced tumor burden and improved survival (P = .2 for both), while rVSV-IL12 monotherapy had better tumor control (P = .06) and survival (P = .024) than combination therapy.
Conclusions:
Addition of cisplatin did not affect the ability of either virus to replicate in or kill murine SCC cells in vitro. In vivo, combination therapy enhancedrVSV-F antitumor activity, but diminished rVSV-IL12 antitumor activity. Combination therapy may provide useful treatment for SCC with the development of more efficient viral vectors in combination with different chemotherapy agents or immunostimulatory agents.
Insights
Combining oncolytic vesicular stomatitis virus (VSV) with cisplatin showed enhanced squamous cell carcinoma (SCC) tumor cell kill in vitro. In vivo, combination therapy improved rVSV-F efficacy but reduced rVSV-IL12 activity against SCC tumors.
Area of Science:
- Oncolytic virotherapy
- Cancer immunotherapy
- Squamous cell carcinoma research
Background:
- Vesicular stomatitis virus (VSV) exhibits oncolytic properties, selectively targeting tumor cells.
- Recombinant VSV vectors, rVSV-F and rVSV-IL12, previously showed antitumor effects against squamous cell carcinoma (SCC).
- Cisplatin is a standard chemotherapeutic agent for SCC.
Purpose of the Study:
- To evaluate the efficacy of combining cisplatin with rVSV-F and rVSV-IL12 for SCC treatment.
- To assess the impact of combination therapy on viral replication, tumor cell survival, tumor control, and animal survival.
Main Methods:
- In vitro studies involved testing rVSV-F and rVSV-IL12 with cisplatin on SCC cell lines, monitoring viral replication and cell viability.
- In vivo studies utilized an orthotopic murine SCC model, administering intratumoral virus injections combined with systemic cisplatin.
- Tumor control and animal survival were assessed in the in vivo model.
Main Results:
- In vitro, the combination of VSV and cisplatin enhanced tumor cell killing without affecting normal human keratinocytes.
- In vivo, combination therapy with rVSV-F and cisplatin reduced tumor burden and improved survival compared to controls.
- However, rVSV-IL12 monotherapy demonstrated superior tumor control and survival rates compared to the combination therapy in vivo.
Conclusions:
- Cisplatin addition did not impede VSV replication or SCC cell killing in vitro.
- Combination therapy augmented rVSV-F antitumor activity but diminished rVSV-IL12 efficacy in vivo.
- Further development of viral vectors and combination strategies may offer improved SCC treatments.
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