SPATIAL AND TEMPORAL CONTROL OF GENE-THERAPY USING IONIZING-RADIATION

Activation of transcription of the Egr-1 gene by X-rays is regulated b y the promoter region of this gene. We linked the radiation-inducible promoter region of the Egr-1 gene to the gene encoding the radiosensit izing and tumoricidal cytokine, tumour necrosis factor-alpha (TNF-alph a) and used a replication-deficient adenovirus to deliver the Egr-TNF construct to human tumours growing in nude mice. Combined treatment wi th AdS.EgrTNF and 5,000 cGy (rad) resulted in increased intratumoral T NF-a production and increased tumour control compared with treatment w ith Ad5.Egr-TNF alone or with radiation alone. The increase in tumour control was achieved without an increase in normal tissue damage when compared to tissue injury from radiation alone. Control of gene transc ription by ionizing radiation in vivo represents a novel method of spa tial and temporal regulation of gene-based medical treatments.