Fusions of the suicide gene Herpes simplex virus type 1 thymidine kinase (HSV-TK) with fluorescent proteins and firefly luciferase were generated to develop improved gene therapeutic strategies for malignant glioma. The optical reporters were tested for their suitability as a measure for the cytotoxic activity of HSV-TK. We showed that the type of the fluorescent protein that was attached to HSV-TK strongly influences localisation, persistence, and activity of the therapeutic transgene. By using bioluminescence imaging we demonstrated that luciferase can indeed be used to quantify therapeutic efficacy of HSV-TK towards human glioblastoma cells in culture and in vivo in nude mice. We proved that combined application of the alkylating agent temozolomide with the ribonucleotide reductase inhibitors didox and trimidox, respectively, results in synergistic cytotoxic effects in several human glioblastoma cell lines. We identified Minichromosome Maintenance Protein 3, a protein essential for DNA replication, as a highly immunogenic tumour-associated antigen and negative prognostic factor in patients with diffuse astrocytoma. The "universal" tumour-specific antigen survivin was shown to be overexpressed in meningioma and glioma and to elicit a high-titered IgG antibody response in brain tumour patients. Expression of at least one of the tumour-specific "cancer testis" antigens MAGE-1, MAGE-3, and NY-ESO-1 was detected in 72% of the examined neuroblastomas, but was of now prognostic value.