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DTA-H19 + PEI is a combination gene therapy consisting of a DNA plasmid encoding the diphtheria toxin A (DTA) chain under the transcriptional control of the human H19 promoter, complexed with the cationic polymer polyethylenimine (PEI) as a gene delivery agent. The therapy is designed to selectively express the DTA toxin in tumor cells with active H19 promoter, causing cell death by inhibition of protein synthesis. The H19 gene is an oncofetal RNA highly expressed in a variety of cancers—including bladder, ovarian, and pancreatic cancers—but is not active in most adult normal tissues. PEI facilitates uptake and delivery of the plasmid DNA into tumor cells. The primary indications under investigation are ovarian, pancreatic, and bladder cancers. Preclinical animal models demonstrated significant inhibition of tumor growth with DTA-H19/PEI treatment, and early-phase clinical trials have studied its safety and efficacy in bladder cancer, with investigational use reported in compassionate cases of ovarian cancer[1][2][4][5][6].
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