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Oncolytic measles viruses encoding interferon beta and the thyroidal sodium iodide symporter gene for mesothelioma

H Li1, K-W Peng, D Dingli

  • 1Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Cancer Gene Therapy
|April 10, 2010
PubMed

Insights

Oncolytic measles viruses (MVs) engineered with interferon beta (IFNbeta) show promise for mesothelioma treatment. These modified MVs enhance immune response and inhibit tumor growth, potentially improving patient survival.

Area of Science:

  • Oncolytic virotherapy
  • Cancer immunology
  • Gene therapy

Background:

  • Mesothelioma has a poor prognosis with limited treatment options.
  • Oncolytic viruses offer a novel therapeutic strategy for cancer.
  • Enhancing oncolytic virus potency is crucial for effective mesothelioma treatment.

Purpose of the Study:

  • To engineer oncolytic measles viruses (MVs) expressing interferon beta (IFNbeta) for enhanced mesothelioma therapy.
  • To evaluate the efficacy of MVs encoding IFNbeta alone or with the sodium iodide symporter (NIS) gene.
  • To investigate the impact of these modified MVs on tumor microenvironment and patient survival.

Main Methods:

  • Insertion of mouse IFNbeta (mIFNbeta) gene, alone or with NIS, into attenuated MV.
  • Propagation and characterization of engineered MVs (MV-mIFNbeta, MV-mIFNbeta-NIS) in human mesothelioma cells.
  • Assessment of viral replication, cell death, IFNbeta production, radioiodine uptake, immune cell infiltration, and angiogenesis in mesothelioma models.

Main Results:

  • Engineered MVs successfully replicated in mesothelioma cells, causing cell death and fusion.
  • High levels of mIFNbeta were detected; MV-mIFNbeta-NIS showed substantial radioiodine uptake.
  • MV-mIFNbeta significantly increased innate immune cell infiltration and reduced tumor angiogenesis.
  • Oncolytic MVs encoding mIFNbeta retarded mesothelioma growth and prolonged survival in tumor models.

Conclusions:

  • Oncolytic MVs expressing IFNbeta are effective in treating mesothelioma.
  • The addition of NIS enhances therapeutic potential, possibly through radioiodine targeting.
  • Engineered MVs represent potent and versatile agents for mesothelioma treatment.

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