title: Development of targeted therapy for a broad spectrum of solid tumors mediated by a double promoter plasmid expressing diphtheria toxin under the control of IGF2-P4 and IGF2-P3 regulatory sequences.
abstract: BACKGROUND
  The human IGF2-P4 and IGF2-P3 promoters are highly active in a variety of human cancers, while existing at a nearly undetectable level in the surrounding normal tissue. Thus, a double promoter DTA-expressing vector was created, carrying on a single construct two separate genes expressing the diphtheria toxin a-fragment (DTA), from two different regulatory sequences, selected from the cancer-specific promoters IGF2-P4 and IGF2-P3.
  
  
  METHODS
  The therapeutic potential of the double promoter toxin vector P4-DTA-P3-DTA was tested in different cancer cells (pancreatic cancer, ovarian cancer and HCC).
  
  
  RESULTS
  The double promoter vector P4-DTA-P3-DTA exhibited superior inhibition activity in different cancer cell lines, compared to the single promoter expression vectors activity.
  
  
  CONCLUSIONS
  Our findings suggest that administration of P4-DTA-P3-DTA has the potential to reach and eradicate tumor cells and thus may help reduce tumor burden, improve the quality of life of the patients; and prolong their life span.
authors: Department of Biological Chemistry, Hebrew University of Jerusalem Jerusalem Israel.
authors: Doron
authors: D
authors: Amit
authors: Sagi
authors: S
authors: Tamir
authors: Abraham
authors: A
authors: Hochberg
keywords: HCC; IGF2; glioblastoma; ovarian cancer; pancreatic cancer; targeted cancer therapy
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