β-galactosidase gene transfer to human malignant glioma

Gene therapy is a promising novel approach to treat malignant brain tumors. Both retro- and adenoviruses have been suggested for gene transfer vectors. In this study we evaluated the efficacy and safety of gene transfer in human malignant glioma. Seven patients with suspected malignant brain tumors according to MRI, underwent stereotactic biopsy to ensure the diagnosis. After confirming the diagnosis by frozen sections, a catheter was inserted into the tumor tissue with the same stereotactic coordinates. Retrovirus (titer 1-5 × 105 cfu/ml) mediated β-galactosidase marker gene transfer was performed for three patients and adenovirus (titer 1-10 × 108 pfu/ml) mediated gene transfer for four patients. The catheter was left in its place and gene transfer was repeated on the first and the second postoperative days. Craniotomy and tumor resection was performed four or five days after the biopsy. Except for one case, tumor was removed in one piece, with catheter still inside the tumor. Tissue samples were stained with x-gal for evaluation of gene transfer efficacy. To study the tissue reactions after the gene transfer tumor samples were immunostained with GFAP, Vimentin, Ki67 and CD68. Our preliminary results show that both retrovirus and adenovirus mediated gene delivery is successful with an expected, low gene transfer efficiency. Gene transfers have been well tolerated and no significant side effects have been observed. The clinical effect of gene therapy is in the first hand dependent on the vector efficiency. Right titer of viruses and necessary precautions in the actual therapy with thymidine kinase gene may be safety evaluated with β-galactosidase gene transfer.