IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Clin Exp Med 2013;6(2):110-118

Original Article
Development of targeted therapy for a broad spectrum of solid tu-mors mediated by
a double promoter plasmid expressing diphtheria toxin under the control of IGF2-P4
and IGF2-P3 regulatory sequences

Doron Amit, Sagi Tamir, Abraham Hochberg

Department of Biological Chemistry, Hebrew University of Jerusalem, Jerusalem Israel

Received October 29, 2012; Accepted December 7, 2012; Epub January 26, 2013; Published February 6, 2013

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 con-struct 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.

Keywords: IGF2, pancreatic cancer, ovarian cancer, glioblastoma, HCC, targeted cancer therapy

Address correspondences to: Dr. Doron Amit, The Department of Biological Chemistry, Institute of Life Sciences, Edmond Safra
Campus, Givat Ram, Jerusalem, Israel, 91904. E-mail: dyamit@gmail.com