) The incidence of primary pediatric brain tumors in the United States is about 1500 per year. Brain tumors are the most common solid tumor diagnosed in childhood and thus account for significant childhood mortality in the United States. A recent pilot trial suggested a possible beneficial effect of the biological response modifier polyICLC in patients with malignant gliomas. This application seeks to determine efficacy of polyICLC in treatment of newly diagnosed pediatric gliomas, including anaplastic astrocytoma (AA), glioblastomas (GBM), and brain stem gliomas, as well as recurrent brain tumors in pediatric patients, and to determine the toxicity of polyICLC in this population. Clinical response to polyICLC will be correlated with tumor histopathology and determine the biological effects of polyICLC on tumor and endothelial cell growth.
The specific aims to accomplish this goal are: 1) a clinical study to determine the efficacy of polyICLC in the treatment of pediatric patients with brain tumors and determine the toxicity of polyICLC in pediatric patients and 2) laboratory studies to determine the biological effects of polyICLC on tumor biology; assess the effects of polyICLC on tumor angiogenesis by immunohistochemical analysis of brain tumor tissue; correlate the efficacy of polyICLC therapy with angiogenic phenotype; determine the effects of polyICLC on human brain microcapillary endothelial cells(HBEC); and evaluate the effects of polyICLC on tumor cell proliferation, cell cycle progression and apoptosis.
