Abstract: The present invention relates to pharmaceutical compositions capable of specifically inducing cell death in the proliferating angiogenic endothelial cells associated with solid tumors and other angiogenesis associated diseases. More specifically, the present invention relates to nucleotide constructs that are selectively active in angiogenic endothelial cells and that encode highly toxic agents, such as diphtheria toxin, for expression in such cells.

Abstract: All lines of mammalian origin which have been stably transformed with a chimeric toxin gene expressed under the regulatory control of HIV cis-acting sequences and HIV trans-acting factors are provided by the present invention. HIV infection of a cell of such a transformed cell line results in the death of that cell due to the specific induction of toxin gene expression within the cell. As specifically exemplified, the toxin gene is the diphtheria toxin fragment A gene or a tox176 fragment A chain gene. Also provided by the present invention are recombinant nucleic acid molecules suitable for the stable transformation of a mammalian cell line to produce a transformed cell which will effectively commit suicide in response to HIV infection due to induction of toxin gene expression.

Abstract: A method for the selective killing of HIV-infected cells, via HIV-regulated expression of a toxin gene, is provided in the present invention. Specifically, the expression of the diphtheria toxin fragment A gene is subject to tight control by cis-acting HIV regulatory sequences and trans-acting regulatory factors. Also provided is a method of protecting a host from HIV infection by the stable transformation of target cells, those cells which can be infected with HIV, with an HIV-regulated toxin gene. When such a stably transformed cell becomes infected with HIV, induction of the toxin gene prevents the replication and spread of the virus.