Abstract
Neural stem cells (NSCs) are capable of tracking migrating glioma cells. To exploit this tropism to generate an antitumor T-cell response, particularly against disseminating tumor pockets, we inoculated intracranial glioma-bearing mice with interleukin 12 (IL-12) producing NSCs. Intratumoral therapy with IL-12-secreting NSCs prolonged survival compared to treatment with nonsecretory NSCs or saline. NSCs demonstrated strong tropism for disseminating glioma, and IL-12-secreting NSC therapy was associated with enhanced T-cell infiltration in tumor microsatellites and long-term antitumor immunity. These results indicate that the use of tumor tracking NSCs represents a potent new therapeutic modality for glioma.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Animals
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Astrocytes / cytology
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Brain Neoplasms / immunology
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Brain Neoplasms / pathology
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Brain Neoplasms / therapy*
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cell Differentiation / physiology
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Cell Movement / physiology
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Glioma / immunology
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Glioma / pathology
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Glioma / therapy*
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Interleukin-12 / immunology
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Interleukin-12 / metabolism*
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Mice
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Mice, Inbred C57BL
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Neurons / cytology
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Neurons / metabolism*
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Neurons / transplantation
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Oligodendroglia / cytology
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Stem Cell Transplantation*
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Stem Cells / metabolism*
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Tumor Cells, Cultured
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beta-Galactosidase / biosynthesis
Substances
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Interleukin-12
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beta-Galactosidase