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AssigneeThe United States of America as represented by the Department of Health and Human Services, National Institutes of Health
InventorsIra Pastan, Vijay K. Chaudhary, David Fitzgerald
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A target-specific, cytotoxic, recombinant Pseudomonas exotoxin is described. Such toxins are made by inserting specific recognition molecules at specific cloning sites in at least domain III near the carboxyl terminus of the PE molecule. Various modifications of the carboxyl terminus of the PE molecule to increase cytotoxicity are set forth. Multifunctional, recombinant, cytotoxic fusion proteins containing at least two different recognition molecules are provided for killing cells expressing receptors to which the recognition molecules bind with specificity. Methods for producing novel recombinant PE molecules with specific properties are described.
A method for killing a target cell, said method comprising contacting said target cell with a cytotoxic amount of a composition comprising a recombinant Pseudomonas exotoxin (PE) having a first recognition molecule for binding said target cell and a carboxyl terminal sequence of 4 to 16 amino acids which permits translocation of the PE molecule into a cytosol of said target cell, the first recognition molecule being inserted in domain III after and no acid 600 and before amino acid 613 of the PE.
A method of killing targeted cells, said method comprising the step of contacting cells targeted to be killed, with a cytotoxic amount of a recombinant Pseudomonas exotoxin fusion protein containing at least two different recognition molecules for killing cells expressing receptors to which said recognition molecules specifically bind.
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