1. ¹Department of Surgery, The University of Chicago Hospitals, Chicago, IL, USA
2. ²Mary Crowley Medical Research Center, Sammons Cancer Center, Dallas, TX, USA
3. ³Department of Medicine, Harvard Medical School, and the Department of Pharmacology, Dana Farber Cancer Institute, Boston Massachusetts, USA
4. ⁴Department of Radiation Oncology, The University of Chicago Hospitals, Chicago, IL, USA

Correspondence: Dr RR Weichselbaum, Department of Radiation and Cellular Oncology, The University of Chicago Hospitals, Center for Advanced Medicine, Room 1329, Mail Code 9006, 5758 South Maryland Avenue, Chicago, IL 60637, USA. E-mail: rrw@rover.uchicago.edu

⁵These two authors contributed equally to this work.

Received 7 February 2005; Revised 20 April 2005; Accepted 1 May 2005; Published online 5 August 2005.

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-. We also summarize the preclinical work and clinical trials utilizing this vector as a treatment for diverse solid tumors.