Immunogene therapy that combines the local administration of dendritic cells pulsed with IL-18 bound by SFV and the systemic administration of IL-12 may be an excellent candidate for the development of a new treatment protocol. A self-replicating SFV system may therefore open a novel approach for the treatment of malignant brain tumor.
In this study, we demonstrate that tumor lysate-loaded dendritic cells can elicit a specific CD8+ cytotoxic T lymphocyte response against autologous tumor cells in patients with malignant glioma. CTL from three of five patients expressed strong cytolytic activity against autologous glioma cells, did not lyse autologous lymphoblasts and were variably cytotoxic against the LAK-sensitive cell line Daudi. Also, DCs pulsed normal brain lysate failed to induce cytolytic activity against autologous glioma cells, suggesting the lack of autoimmune response. Two of five patients CD8+ T cells expressed a modest cytotoxicity against autologous glioma cells. CD8+ T cells isolated during these ineffective primings secreted large amounts of IL-10, less amounts of IFN-gamma as detected by ELISA, Type 2 bias in the CD8+ T cell response accounts for the lack of cytotoxic effector function from these patients. Cytotoxicity against autologous glioma cells could be significantly inhibited by anti-HLA class I antibody. These data demonstrate that tumor lysate-loaded DC can be an effective tool in inducing glioma-specific CD8+ CTL able to kill autologous glioma cells in vitro. However, high levels of tumor specific tolerance in some patients may account for a significant barrier to therapeutic vaccination. Moreover, cytotoxic responses were augmented by transfecting DC with the gene for IL-18. For all five patients, CD8+T cells treated with IL18 transfected DC produced Th1 response. These results may have important implications for the treatment of malignant glioma patients with immunotherapy. DCs loaded with total tumor lysate and IL-18 may represent a method for inducing Th1 immunoresponses against the entire repertoire of glioma antigens.
Immunogene therapy combined with DC therapy, IL-12, and IL-18 may be an excellent candidate in the development of a new treatment protocol. The self-replicating SFV system may therefore provide a novel approach for the treatment of malignant gliomas.
Intracranial lipomas are believed to be congenital malformations rather than true neoplasms, resulting from the abnormal differentiation of the meninx primitiva, the undifferentiated mesenchyme. We report here the surgical pathological features of a lipoma that was located on the cerebral surface of an abnormally formed fissure, and the underlying cortex of the middle temporal gyrus of a 20-year-old woman. The mass was composed of typical adipose tissue in which a large number of blood vessels were present. Thick connective tissue associated with the arachnoid membrane covered the cortical surface. The cortex exhibited a polymicrogyric configuration in which the cortical ribbon was abnormally undulated and excessively folded. Reelin-immunolabeled Cajal-Retzius-cell-like cells were observed frequently in the fused molecular layer. The cortical lamination underlying the molecular layer was poorly defined. Along the border between the connective tissue and cortical surface, there was a narrow zone in which the mesenchymal and neuronal tissues were intermingled, and where immunohistochemical and ultrastructural investigations disclosed disruption of the basal lamina, prominent astrocytosis, and abundant axonal and synaptic profiles. These findings suggest that focal disturbances in cerebral cortical development occur in association with the development of lipomas.
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