Related Experiment Video
Updated: Mar 25, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Variation in susceptibility of human malignant melanomas to oncolytic vesicular stomatitis virus
Aaron U Blackham1, Scott A Northrup, Mark Willingham
1Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Background:
Vesicular stomatitis virus (VSV) is a novel, anti-cancer therapy that targets cancer cells selectively with defective antiviral responses; however, not all malignant cells are sensitive to the oncolytic effects of VSV. Herein, we have explored the mechanistic determinants of mutant M protein VSV (M51R-VSV) susceptibility in malignant melanoma cells.
Methods:
Cell viability after VSV infection was measured by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) viability assay in a panel of melanoma cell lines. VSV infectability, viral protein synthesis, and viral progeny production were quantified by flow cytometry, (35)S-methionine electrophoresis, and viral plaque assays, respectively. Interferon (IFN) responsiveness was determined using MTS assay after β-IFN pretreatment. Xenografts were established in athymic nude mice and treated with intratumoral M51R-VSV.
Results:
Cell viability after M51R-VSV infection at a multiplicity of infection of 10 pfu/mL, 48 hours postinfection) ranged between 0 ± 1% and 59 ± 9% (mean ± standard deviation). Sensitive cell lines supported VSV infection, viral protein synthesis, and viral progeny production. In addition, when pretreated with β-IFN, sensitive cells became resistant to M51R-VSV, suggesting that IFN-mediated antiviral signaling is defective in these cells. In contrast, resistant melanoma cells do not support VSV infection, viral protein synthesis, or viral replication, indicating that antiviral defenses remain intact. In a murine xenograft model, intratumoral M51R-VSV treatment decreased tumor growth relative to controls after 26 days in SK-Mel 5 (-21 ± 19% vs. 2,100 ± 770%; P < .0001) and in SK-Mel 3 (2,000 ± 810% vs. 7,000 ± 3,000%; P = .008) established tumors.
Conclusion:
M51R-VSV is a viable anti-cancer therapy, but susceptibility varies among melanomas. Future work will exploit specific mechanisms of resistance to expand the therapeutic efficacy of M51R-VSV.
Insights
Mutant M protein VSV (M51R-VSV) shows promise as an anti-cancer therapy for melanoma. However, its effectiveness varies, with sensitive cells supporting viral replication while resistant cells maintain intact antiviral defenses.
Area of Science:
- Oncolytic virology
- Cancer therapeutics
- Melanoma research
Background:
- Vesicular stomatitis virus (VSV) is an emerging anti-cancer therapy targeting cancer cells with defective antiviral responses.
- Not all malignant cells are sensitive to VSV's oncolytic effects, necessitating investigation into resistance mechanisms.
- This study explores the determinants of mutant M protein VSV (M51R-VSV) susceptibility in malignant melanoma cells.
Purpose of the Study:
- To investigate the mechanistic basis of M51R-VSV susceptibility and resistance in melanoma cell lines.
- To evaluate the anti-cancer efficacy of M51R-VSV in a preclinical melanoma model.
Main Methods:
- Cell viability was assessed using the MTS assay post-M51R-VSV infection.
- VSV infectability, protein synthesis, and progeny production were quantified via flow cytometry, electrophoresis, and plaque assays.
- Interferon (IFN) responsiveness was tested, and M51R-VSV efficacy was evaluated in murine xenografts.
Main Results:
- M51R-VSV exhibited variable efficacy, with sensitive melanoma cell lines supporting viral replication and resistant lines showing intact antiviral defenses.
- Interferon pretreatment rendered sensitive cells resistant, indicating defective IFN-mediated antiviral signaling.
- Intratumoral M51R-VSV treatment significantly reduced tumor growth in murine xenograft models.
Conclusions:
- M51R-VSV is a potential anti-cancer therapy for melanoma, but its efficacy is dependent on melanoma cell susceptibility.
- Understanding and overcoming resistance mechanisms is crucial for expanding the therapeutic potential of M51R-VSV.
Related Concept Videos
01:03Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
01:03Rous Sarcoma Virus (RSV) and Cancer