Cytotoxins comprising modified bouganin toxin for the treatment of cancer

Abstract

The invention provides modified forms of bouganin protein having biological activity and a reduced propensity to activate human T cells as compared to the non-modified bouganin protein. The invention also provides T-cell epitope peptides of bouganin, and modified T-cell epitope peptides of bouganin which have a reduced propensity to activate human T cells as compared to the non-modified T-cell epitope peptide. The invention also provides cytotoxins having the having a ligand that binds to a cancer cells attached to the modified bouganin proteins. Also provided are methods of inhibiting or destroying mammalian cancer cells using the cytotoxins of the invention and pharmaceutical compositions for treating human cancer.

What is claimed is: 
     
         1 . An immunotoxin comprising a first polypeptide having an amino acid sequence from amino acid 23 to amino acid 503 of SEQ ID NO: 16, and a second polypeptide having an amino acid sequence from amino acid 532 to amino acid 750 of SEQ ID NO: 16, and the first polypeptide and the second polypeptide are linked by a di-sulfide bond. 
     
     
         2 . The immunotoxin of  claim 1 , wherein the immunotoxin is a modified bouganin protein linked to a Fab antibody fragment that binds to Ep-CAM. 
     
     
         3 . An immunotoxin comprising a first polypeptide having an amino acid sequence from amino acid 29 to amino acid 247 of SEQ ID NO: 20, and a second polypeptide having an amino acid sequence from amino acid 270 to amino acid 750 of SEQ ID NO: 20, and the first polypeptide and the second polypeptide are linked by a di-sulfide bond. 
     
     
         4 . The immunotoxin of  claim 3 , wherein the immunotoxin is a modified bouganin protein linked to a Fab antibody fragment that binds to Ep-CAM. 
     
     
         5 . An immunotoxin comprising a first polypeptide having an amino acid sequence from amino acid 23 to amino acid 503 of SEQ ID NO: 22, and a second polypeptide having an amino acid sequence from amino acid 532 to amino acid 750 of SEQ ID NO: 22, and the first polypeptide and the second polypeptide are linked by a di-sulfide bond. 
     
     
         6 . The immunotoxin of  claim 5 , wherein the immunotoxin is a modified bouganin protein linked to a Fab antibody fragment that binds to Ep-CAM. 
     
     
         7 . An immunotoxin comprising a first polypeptide having an amino acid sequence from amino acid 29 to amino acid 247 of SEQ ID NO: 24, and a second polypeptide having an amino acid sequence from amino acid 270 to amino acid 750 of SEQ ID NO: 24, and the first polypeptide and the second polypeptide are linked by a di-sulfide bond. 
     
     
         8 . The immunotoxin of  claim 7 , wherein the immunotoxin is a modified bouganin protein linked to a Fab antibody fragment that binds to Ep-CAM.