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Updated: May 12, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Primary resistance phenomena to oncolytic measles vaccine viruses
Markus Noll1, Susanne Berchtold, Johanna Lampe
1Department of Internal Medicine I, University Hospital Tübingen, D-72076 Tübingen, Germany.
Abstract:
Measles vaccine virus (MeV) has been shown to possess profound oncolytic capabilities. However, tumor cell resistance to MeV may endanger broad clinical success. Here, this hypothesis is underlined by our analysis of the NCI-60 tumor cell panel infected with a suicide gene-armed MeV vector (MeV-SCD). Quantification of the MeV-SCD-induced oncolytic effect exhibited a 50% rate of NCI-60 solid tumor cell lines being susceptible to MeV-SCD induced oncolysis. In contrast, nearly 40% of the NCI-60 tumor cell lines had to be categorized as partially resistant (exhibiting 50-75% remnant tumor cells) and six tumor cell lines even showed high resistance to MeV-SCD-induced oncolysis with remnant tumor cell masses >75%. According to our further analysis, these high-grade resistant tumor cell lines i) exhibited a high variation in primary infectability rates and also different patterns of alterations ii) in virus replication and iii) in interferon response. This diversity of virotherapy resistance phenomena seems to go along with the diversity of genetic and epigenetic changes accompanying malignant transformation. Of paramount clinical importance, this plethora of resistance phenomena was shown to be overcome in vitro by employment of an increased MOI together with addition of the prodrug 5-FC, thus exploiting the highly efficient suicide gene function of vector MeV-SCD used in this study.
Insights
Measles vaccine virus (MeV) shows oncolytic potential, but tumor resistance limits success. Combining MeV with a suicide gene and prodrug overcomes resistance in resistant cancer cells.
Area of Science:
- Oncology
- Virology
- Gene Therapy
Background:
- Measles vaccine virus (MeV) exhibits significant oncolytic capabilities against cancer cells.
- Tumor cell resistance to MeV poses a challenge for its widespread clinical application in cancer therapy.
Purpose of the Study:
- To investigate the susceptibility of the NCI-60 tumor cell panel to MeV armed with a suicide gene (MeV-SCD).
- To analyze the mechanisms of tumor resistance to MeV-SCD and explore strategies to overcome it.
Main Methods:
- Infection of the NCI-60 tumor cell panel with MeV-SCD.
- Quantification of oncolysis and categorization of tumor cell resistance levels.
- Analysis of infectability, virus replication, and interferon response in resistant cell lines.
- In vitro testing of combined therapy using increased multiplicity of infection (MOI) and 5-FC prodrug.
Main Results:
- 50% of NCI-60 cell lines were susceptible to MeV-SCD induced oncolysis.
- Approximately 40% of cell lines showed partial resistance, and six exhibited high resistance (>75% remnant tumor cells).
- High resistance correlated with variations in infectability, viral replication, and interferon response, linked to genetic/epigenetic changes.
- Increased MOI combined with 5-FC prodrug effectively overcame MeV-SCD resistance in vitro.
Conclusions:
- Tumor cell resistance to MeV-SCD is diverse and multifactorial, influenced by intrinsic cellular properties.
- The combination of MeV-SCD with 5-FC prodrug represents a promising strategy to overcome resistance and enhance oncolytic virotherapy efficacy.
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