NCIt definition : A plasmid DNA encoding the A chain of the diphtheria toxin (DT-A) driven by the transcriptional
regulatory sequences of human H19, with potential antineoplastic activity. Because
the expression of DT-A is under the control of H19 promotor elements, DT-A is selectively
expressed in tumor cells capable of turning on H-19. DT-A catalyzes ADP-ribosylation
of translation elongation factor 2 (EF-2), resulting in the inhibition of protein
synthesis and apoptosis. In addition, DT-A protein released from lysed cells cannot
enter and kill neighboring cells because of the absence of the DT-B chain, further
enhancing the selective cytotoxicity of this agent. Human H19 is a paternally-imprinted,
oncofetal gene encoding an RNA product; it acts as a riboregulator in gene expression
and is found at substantial levels in different human tumor cell types while its expression
in normal adult tissue is limited.;