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.

نویسندگان

  • Doron Amit
  • Sagi Tamir
  • Abraham Hochberg
چکیده

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.

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Development of targeted therapy for a broad spectrum of cancers (pancreatic cancer, ovarian cancer, glioblastoma and HCC) mediated by a double promoter plasmid expressing diphtheria toxin under the control of H19 and IGF2-P4 regulatory sequences.

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عنوان ژورنال:
  • International journal of clinical and experimental medicine

دوره 6 2  شماره 

صفحات  -

تاریخ انتشار 2013