Immunotoxins directed against CD33 related surface antigens

Abstract

The present invention provides novel immunotoxins and methods of treating neoplastic diseases. These immunotoxins are comprised of a conjugation of an antigen binding region exhibiting binding specificity for the CD33 protein and a cell growth modulator. The immunotoxins of the present invention specifically and selectively kill tumor cells that are characterized by the expression of CD33 antigen. Thus, the novel immunotoxins would be useful in treating human leukemias, both acute and chronic, and other myelodysplastic syndromes.

1 . A composition comprising an antibody or antibody fragment that binds to CD33 protein conjugated to a toxin.  
     
     
         2 . The composition of  claim 1 , wherein said binding specificity is for an extracellular epitope of CD33.  
     
     
         3 . The composition of  claim 1 , wherein said protein exhibiting binding specificity for an antigen domain for CD33 protein is a single chain antibody.  
     
     
         4 . The composition of  claim 1 , wherein said protein exhibiting binding specificity for an antigen domain for CD33 protein is selected from the group consisting of murine monoclonal antibodies, humanized monoclonal antibodies and chimeric antibodies.  
     
     
         5 . (canceled)  
     
     
         6 . The composition of  claim 1  further comprising a pharmaceutically acceptable carrier.  
     
     
         7 . A single dose composition of  claim 6 .  
     
     
         8 . A method of treating a neoplastic cell comprising administering to said cell a therapeutically effective dose of the composition of  claim 6 .  
     
     
         9 . The method of  claim 8 , wherein said cell is selected from the group consisting of acute and chronic myeloid leukemias, acute and chronic myelodysplastic syndromes, refractory anemias, lymphoid leukemias and undifferentiated leukemias.  
     
     
         10 . The method of  claim 8 , wherein said composition retards the rate of growth of said cells.  
     
     
         11 . The method of  claim 8 , wherein said neoplastic cell is in a human or non-human.  
     
     
         12 . The method of  claim 8 , wherein said composition prevents recurrence of a neoplastic condition.  
     
     
         13 . The method of  claim 8 , wherein said composition extends the survival time of a host of said neoplastic cell.  
     
     
         14 . The method of  claim 8 , wherein said neoplastic cell is in vitro.  
     
     
         15 . The method of  claim 8 , wherein said neoplastic cell is in bone marrow.  
     
     
         16 - 17 . (canceled)  
     
     
         18 . The composition of  claim 1 , wherein the toxin is recombinant gelonin or a functionally active recombinant gelonin fragment.  
     
     
         19 . The composition of  claim 1 , wherein the toxin is abrin, ricin, or modeccin.  
     
     
         20 . A method of killing a tumor cell in a subject, comprising administering to the subject a pharmaceutically effective amount of a composition comprising an antibody or antibody fragment that binds to CD33 protein conjugated to a toxin.  
     
     
         21 . The method of  claim 20 , wherein the toxin is recombinant gelonin or a functionally active recombinant gelonin fragment.  
     
     
         22 . The method of  claim 20 , wherein the toxin is abrin, ricin, or modeccin.  
     
     
         23 . The composition of  claim 19 , wherein the toxin is abrin.  
     
     
         24 . The composition of  claim 19 , wherein the toxin is ricin.  
     
     
         25 . The composition of  claim 19 , wherein the toxin is modeccin.