Abstract
Gene therapy of cancer represents a promising but challenging area of therapeutic research. The discovery of radiation-inducible genes led to the concept and development of radiation-targeted gene therapy. In this approach, promoters of radiation-inducible genes are used to drive transcription of transgenes in the response to radiation. Constructs in which the radiation-inducible promoter elements activate a transgene encoding a cytotoxic protein are delivered to tumors by adenoviral vectors. The tumoricidal effects are then localized temporally and spatially by X-rays. We review the conceptual development of TNFerade™, an adenoviral vector containing radiation-inducible elements of the early growth response-1 promoter upstream of a cDNA encoding human tumor necrosis factor-α. We also summarize the preclinical work and clinical trials utilizing this vector as a treatment for diverse solid tumors.
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Acknowledgements
This research was sponsored in part by the Varian corporation and the University of Chicago Center for Radiation Therapy.
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GenVec Inc. provided the adenoviral vectors used in the studies reported herein. RRW and DWK are consultants for GenVec Inc. and hold interest in the company.
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Mezhir, J., Smith, K., Posner, M. et al. Ionizing radiation: a genetic switch for cancer therapy. Cancer Gene Ther 13, 1–6 (2006). https://doi.org/10.1038/sj.cgt.7700879
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DOI: https://doi.org/10.1038/sj.cgt.7700879