Suicidal gene therapy in an NF-B-controlled tumor environment as monitored by a secreted blood reporter

C. E. Badr, J. M. Niers, D. Morse, J. A. Koelen, P. Vandertop, D. Noske, T. Wurdinger, P. A. Zalloua, B. A. Tannous

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


The nuclear factor-B (NF-B) is known to be activated in many cancer types including lung, ovarian, astrocytomas, melanoma, prostate as well as glioblastoma, and has been shown to correlate with disease progression. We have cloned a novel NF-B-based reporter system (five tandem repeats of NF-B responsive genomic element (NF; 14 bp each)) to drive the expression cassette for both a fusion between the yeast cytosine deaminase and uracil phosphoribosyltransferase (CU) as a therapeutic gene and the secreted Gaussia luciferase (Gluc) as a blood reporter, separated by an internal ribosomal entry site (NF-CU-IGluc). We showed that malignant tumor cells have high expression of Gluc, which correlates to high activation of NF-B. When NF-B was further activated by tumor necrosis factor-α in these cells, we observed up to 10-fold increase in Gluc levels and therefore transgene expression in human glioma cells served to greatly enhance the sensitization of these cells to the prodrug, 5-fluorocytosine both in cultured cells and in vivo subcutaneous tumor xenograft model. This inducible system provides a tool to enhance the expression of imaging and therapeutic genes for cancer therapy.

Original languageBritish English
Pages (from-to)445-451
Number of pages7
JournalGene Therapy
Issue number5
StatePublished - May 2011


  • blood reporter
  • cytosine deaminase
  • Gaussia luciferase
  • nuclear factor-κB
  • Suicidal gene therapy
  • uracil phosphoribosyltransferase


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