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: Doron Amit, Sagi Tamir, Abraham Hochberg
• Journal: International journal of clinical and experimental medicine (Int J Clin Exp Med) Vol. 6 Issue 2 Pg. 110-8 ( 2013) ISSN: 1940-5901 [Print] United States
• PMID: 23386914 (Publication Type: Journal Article)