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Current status of gene therapy for brain tumors

  • Andrea M. Murphy
    Affiliations
    Brain Tumor Research Center, Molecular Neurosurgery Laboratory, Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, Mass
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  • Samuel D. Rabkin
    Correspondence
    Reprint requests: Samuel D. Rabkin, PhD, Brain Tumor Research Center, Molecular Neurosurgery Laboratory, Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, 185 Cambridge St, CPZN-3800, Boston, MA 02114.
    Affiliations
    Brain Tumor Research Center, Molecular Neurosurgery Laboratory, Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, Mass
    Search for articles by this author
Published:December 13, 2012DOI:https://doi.org/10.1016/j.trsl.2012.11.003
      Glioblastoma (GBM) is the most common and deadliest primary brain tumor in adults, with current treatments having limited impact on disease progression. Therefore the development of alternative treatment options is greatly needed. Gene therapy is a treatment strategy that relies on the delivery of genetic material, usually transgenes or viruses, into cells for therapeutic purposes, and has been applied to GBM with increasing promise. We have included selectively replication-competent oncolytic viruses within this strategy, although the virus acts directly as a complex biologic anti-tumor agent rather than as a classic gene delivery vehicle. GBM is a good candidate for gene therapy because tumors remain locally within the brain and only rarely metastasize to other tissues; the majority of cells in the brain are post-mitotic, which allows for specific targeting of dividing tumor cells; and tumors can often be accessed neurosurgically for administration of therapy. Delivery vehicles used for brain tumors include nonreplicating viral vectors, normal adult stem/progenitor cells, and oncolytic viruses. The therapeutic transgenes or viruses are typically cytotoxic or express prodrug activating suicide genes to kill glioma cells, immunostimulatory to induce or amplify anti-tumor immune responses, and/or modify the tumor microenvironment such as blocking angiogenesis. This review describes current preclinical and clinical gene therapy strategies for the treatment of glioma.

      Abbreviations:

      Ad (adenoviruses), Ad5 (adenovirus serotype 5), CD (cytosine deaminase), CEA (carcinoembryonic antigen), CRAds (conditionally-replicative adenoviruses), 5-FC (5-fluorocytosine), Flt3L (fms-like tyrosine kinase ligand), GBM (glioblastoma), GCV (ganciclovir), GM-CSF (granulocyte macrophage colony stimulating factor), GSCs (glioblastoma stem cells), HSV (herpes simplex virus), MSCs (mesenchymal stromal (stem) cells), MV (measles virus), MV-CEA (measles virus expressing the human carcinoembryonic antigen), MV-NIS (measles virus expressing the sodium iodide symporter), NDV (Newcastle disease virus), NSCs (neural stem cells), oHSV (oncolytic herpes simplex virus), PNP (purine nucleoside phosphorylase), PV (poliovirus), RCRs (replication-competent gamma-retroviruses), tk or TK (thymidine kinase), TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), VEGF (vascular endothelial growth factor), VSV (vesticular stomatitis virus), VV (vaccinia virus)
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