DTAT fusion toxin

Abstract

The invention provides fusion toxins that contain one or more regions of diphtheria toxin and a portion of urokinase-type plasminogen activator, as well as the nucleic acids that encode the fusion toxins and methods of using the fusion toxins.

1 . A method for killing a tumor cell, comprising contacting said tumor cell with a fusion toxin comprising the toxin domain of diphtheria toxin and a urokinase-type plasminogen activator domain.  
   
   
       2 . The method of  claim 1 , wherein said tumor cell is a brain tumor cell.  
   
   
       3 . The method of  claim 2 , wherein said brain tumor is selected from the group consisting of glioblastoma, meningioma, astrocytoma, medulloblastoma, ependymoma, and oligodendroglioma.  
   
   
       4 . The method of  claim 2 , wherein said brain tumor is a glioblastoma.  
   
   
       5 . The method of  claim 1 , wherein said tumor cell expresses the urokinase-type plasminogen activator receptor.  
   
   
       6 . The method of  claim 1 , wherein contacting said tumor cell occurs in vivo.  
   
   
       7 . The method of  claim 1 , wherein said fusion toxin comprises the translocation enhancer region of diphtheria toxin.  
   
   
       8 . The method of  claim 1 , wherein said fusion toxin comprises the amino terminal 390 amino acids of diphtheria toxin.  
   
   
       9 . The method of  claim 1 , wherein said urokinase-type plasminogen activator domain is capable of binding to urokinase-type plasminogen activator receptor.  
   
   
       10 . The method of  claim 9 , wherein said urokinase-type plasminogen activator domain comprises the amino terminal fragment of urokinase-type plasminogen activator.  
   
   
       11 . The method of  claim 1 , wherein said fusion toxin comprises the toxin domain of diphtheria toxin, the translocation enhancing region of diphtheria toxin, and the amino-terminal fragment of urokinase-type plasminogen activator.  
   
   
       12 . A method for killing a glioblastoma tumor cell, comprising contacting said glioblastoma tumor cell with a fusion toxin comprising a urokinase-type plasminogen activator domain.  
   
   
       13 . The method of  claim 12 , wherein said fusion toxin comprises a toxin domain of a toxin selected from the group consisting of diphtheria toxin, ricin,  Pseudomonas  exotoxin, colicin, anthrax toxin, tetanus toxin, botulinum neurotoxin, saporin, abrin, bryodin, pokeweed anti-viral protein, viscumin, and gelonin.  
   
   
       14 . The method of  claim 12 , wherein said fusion toxin comprises the toxin domain of diphtheria toxin.  
   
   
       15 . The method of  claim 12 , wherein said fusion toxin comprises an internalization domain of a toxin selected from the group consisting of diphtheria toxin, colicin, delta-Endotoxin, anthrax toxin, tetanus toxin, botulinum toxin, and  Pseudomonas  exotoxin.  
   
   
       16 . The method of  claim 12 , wherein said fusion toxin comprises the translocation enhancing region of diphtheria toxin.  
   
   
       17 . The method of  claim 12 , wherein said urokinase-type plasminogen activator domain is capable of binding to urokinase-type plasminogen activator receptor.  
   
   
       18 . The method of  claim 17 , wherein said urokinase-type plasminogen activator domain comprises the amino-terminal fragment of urokinase-type plasminogen activator.  
   
   
       19 . The method of  claim 12 , wherein said glioblastoma tumor cell expresses the urokinase-type plasminogen activator receptor.  
   
   
       20 . The method of  claim 12 , wherein said fusion toxin comprises the toxin domain of diphtheria toxin, the translocation enhancing region of diphtheria toxin, and the amino-terminal fragment of the urokinase-type plasminogen activator.  
   
   
       21 .- 29 . (canceled)