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By Frans Antonie Stafleu

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Although the efficiency of HSV 1-TK and GCV has been shown in a large variety of experimental models, the clinical results, while encouraging, remain inconclusive. The main reason thought to underlie this difference is the low levels of HSV1-TK expression from currently available vectors. Our experiments will address this issue by vastly increasing therapeutic transgene expression (through the use of a novel promoter) and reducing the viral vector toxicity (through the use of novel safer vectors of reduced toxicity).

2)To determine the gene expression profiles of 120 excisional glioma and meningioma brain tumor biopsies to develop a reclassification of the tumors based on gene expression profiles. 3)To develop a set of genes with prognostic importance in low grade astrocytomas. 4)To validate the importance of the genes from specific aims 2 and 3 in the prognosis of low grade astrocytomas. Generate_Screen • Project Title: GENE THERAPY FOR BRAIN TUMORS USING ANTISENSE CDNA TRANSCRIPTION GROW Principal Investigator & Institution: Ilan, Joseph; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001 Summary: This study represents a treatment approach based on an antisense gene therapy strategy for otherwise incurable malignant human brain tumors.

Whitley will focus on the generation of viruses with enhanced oncolytic potential for human gliomas. They will determine whether viruses selected with novel properties demonstrate enhanced Studies 25 neurovirulent properties. New viruses and treatment enhancing discoveries will be funneled into Markert, which will begin the process of translating genetically engineered viruses to clinical trials. 5 HSV that expresses Interleukin-12 was constructed during the initial period of funding and will be the first candidate virus to be advanced into Phase I clinical trials.

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