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

International Journal of Clinical and Experimental Medicine

Abraham Hochberg¹  Doron Amit¹ 

关键词: IGF2;    H19;    pancreatic cancer;    ovarian cancer;    glioblastoma;    hepatocellular carcinoma;    diphtheria toxin A;    targeted cancer therapy;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

The human IGF2-P4 and H19 promoters are highly active in a variety of human cancers, while existing at a nearly undetectable level in the surrounding normal tissue. Single promoter vectors expressing diphtheria toxin A-fragment (DTA) under the control regulation of IGF2-P4 or H19 regulatory sequences (IGF2-P4-DTA and H19-DTA) were previously successfully used in cell lines, animal models and recently in human patients with superficial cell carcinoma of the bladder, pancreatic cancer and ovarian cancer (treated with H19-DTA). However this targeted medicine approach may be limited, as not all cancer patients express high levels of H19 and it requires prerequisite diagnostic test for H19. Hence, 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 H19 and IGF2-P4.

【 授权许可】

Unknown