Neoplastic Brain, Glioblastoma, and Immunotherapy

Abstract

IGF-I, insulin-like growth factor 1, is present in normal fetal/neonatal brain development and reappears in the mature brain participating in the development of malignant tumor, glioblastoma multiforme. Targeting the IGF-I system has emerged as a useful method to reduce glial malignant development. Downregulation in the expression of IGF-I using antigene anti-IGF-I technology (antisense, AS, and triple helix, TH) applied in glioma cell culture established from glioblastoma biopsies induces the expression of B7 and MHC-I antigens in transfected cells (immunogenicity). The transfected cancer cells, "vaccines," after subcutaneous injection, initiated an immune response mediated by T CD8+ lymphocytes, followed by tumor regression (immunotherapy). The median survival of patients treated by surgery followed by radiotherapy and immunotherapy was 21-24 months. On the other side, the experimental work has demonstrated that IGF-I AS or TH transfected tumor cells fused with activated dendritic cells, DC, showing more striking immunogenic character. Using IGF-I TH/DC "vaccination," the efficiency in suppressing rat glioma tumors is not only relatively higher than that obtained using IGF-I TH cells but is also more rapid.

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