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Neural Stem Cell-based Gene Therapy for Brain Tumors

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Abstract

Advances in gene-based medicine since 1990s have ushered in new therapeutic strategy of gene therapy for inborn error genetic diseases and cancer. Malignant brain tumors such as glioblastoma multiforme and medulloblastoma remain virtually untreatable and lethal. Currently available treatment for brain tumors including radical surgical resection followed by radiation and chemotherapy, have substantially improved the survival rate in patients suffering from these brain tumors; however, it remains incurable in large proportion of patients. Therefore, there is substantial need for effective, low-toxicity therapies for patients with malignant brain tumors, and gene therapy targeting brain tumors should fulfill this requirement. Gene therapy for brain tumors includes many therapeutic strategies and these strategies can be grouped in two major categories: molecular and immunologic. The widely used molecular gene therapy approach is suicide gene therapy based on the conversion of non-toxic prodrugs into active anticancer agents via introduction of enzymes and genetic immunotherapy involves the gene transfer of immune-stimulating cytokines including IL-4, IL-12 and TRAIL. For both molecular and immune gene therapy, neural stem cells (NSCs) can be used as delivery vehicle of therapeutic genes. NSCs possess an inherent tumor tropism that supports their use as a reliable delivery vehicle to target therapeutic gene products to primary brain tumors and metastatic cancers throughout the brain. Significance of the NSC-based gene therapy for brain tumor is that it is possible to exploit the tumor-tropic property of NSCs to mediate effective, tumor-selective therapy for primary and metastatic cancers in the brain and outside, for which no tolerated curative treatments are currently available.

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Acknowledgements

The author thanks Drs. K. Aboody, M. Danks, S.K. Kim, D.H. Nam, A. Natsume and H.J. Lee for their contributions to the works cited in the article. This work was supported by grants from the Canadian Myelin Research Initiative and the National R&D Program for Cancer Control, Korean Ministry for Health, Welfare and Family affairs (20090403).

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  1. Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, BC, V6T 2B5, Canada

    Seung U. Kim

  2. Medical Research Institute, Chung-Ang University College of Medicine, Seoul, South Korea

    Seung U. Kim

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Kim, S.U. Neural Stem Cell-based Gene Therapy for Brain Tumors. Stem Cell Rev and Rep 7, 130–140 (2011). https://doi.org/10.1007/s12015-010-9154-1

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