BC-819, a plasmid comprising the H19 gene regulatory sequences and diphtheria toxin A, for the potential targeted therapy of cancers.

BC-819 (DTA-H19), in development by BioCancell Therapeutics Inc, under license from the Hebrew University of Jerusalem, is a double-stranded DNA plasmid carrying the gene for the A subunit of diphtheria toxin under the regulation of the H19 gene promoter. H19, a paternally imprinted, oncofetal gene, encodes an RNA that acts as a riboregulator. Expressed at substantial levels in embryonic and malignant tissues, but minimally or not expressed in adult tissues, elevated H19 RNA expression has been observed in over 30 malignancies prompting investigation into its utility as a targeted therapeutic agent. While most in vivo studies have investigated BC-819 for the treatment of bladder cancer, recent studies have also yielded encouraging results in NSCLC,colon, pancreatic and ovarian cancers. A phase I/IIa clinical trial in patients with non-muscle invasive bladder cancer receiving intravesical BC-819 reported mild local toxicity and complete and partial response rates of 22 and 44%, respectively. At the time of publication, a phase IIb trial was ongoing in patients with bladder cancer, while phase I/II clinical trials in patients with ovarian and pancreatic cancer were accruing participants. This review provides a focused summary of the existing experimental evidence demonstrating the effectiveness of the plasmid construct, early clinical outcomes and a discussion of the potential role of BC-819 as a targeted cancer therapy.