The United States of America, as Represented by the Secretary, Department of Health and Human Services

Thomas H Bugge

Stephen H Leppla

Shi-Hui Liu

Henning Birkedal-Hansen

Sarah Netzel-Arnett

Diane E Peters

Jie Liu

Alexander N Wein

Kuang-Hua Chen

Disclosed is aprotective antigen (PA) comprising a PA amino acid sequence, wherein one or more of amino acid residues I207, I210, E654, I656, R659, M662, Y681, and L687, as defined by reference to SEQ ID NO: 1, are, independently, substituted, with the proviso that amino acid residue I207 is not substituted with alanine and amino acid residue I210 is not substituted with alanine. Related compositions, nucleic acids, recombinant expression vectors, host cells, populations of cells, methods of treating or preventing cancer in a mammal, and methods of inhibiting the growth of a target cell are also disclosed.

Modified anthrax toxin protective antigen

The present invention provides methods of specifically targeting compounds to cells overexpressing matrix metalloproteinases, plasminogen activators, or plasminogen activator receptors, by administering a compound and a mutant protective antigen protein comprising a matrix metalloproteinase or a plasminogen activator-recognized cleavage site in place of the native protective antigen furin-recognized cleavage site, wherein the mutant protective antigen is cleaved by a matrix metalloproteinase or a plasminogen activator overexpressed by the cell, thereby translocating into the cell a compound comprising a lethal factor polypeptide comprising a protective antigen binding site.

Mutated anthrax toxin protective antigen proteins that specifically target cells containing high amounts of cell-surface metalloproteinases or plasminogen activator receptors

The present invention provides compositions comprising modified bacterial toxins and methods for using the modified bacterial toxins for targeting particular cell populations and for treating diseases.

Multimeric protein toxins to target cells having multiple identifying characteristics

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Bethesda, MD, United States of America

Thomas H Bugge