Immunotoxins directed against malignant cells

Abstract

The present invention relates to immunotoxins, that effectively kill malignant cells having a given surface marker and nucleic acid constructs encoding them. These reagents comprise a toxic moiety that is derived from a Rana pipiens protein having ribonucleolytic activity linked to an antibody capable of specific binding with a chosen tumor cell.

1 - 34 . (canceled)  
     
     
         35 . A selective cytotoxic reagent comprising an onc protein having measurable ribonucleolytic activity covalently linked to an antibody directed against a surface marker specific to a B cell.  
     
     
         36 . The reagent of  claim 35 , wherein the onc protein has the amino acid sequence of SEQ ID NO:1.  
     
     
         37 . The reagent of  claim 35 , wherein the onc protein is produced by recombinant means.  
     
     
         38 . The reagent of  claim 37 , wherein the onc protein has the amino acid sequence of SEQ ID NO:3  
     
     
         39 . The reagent of  claim 35 , wherein the antibody is a monoclonal antibody.  
     
     
         40 . The reagent of  claim 39 , wherein the monoclonal antibody is humanized.  
     
     
         41 . The reagent of  claim 40 , wherein the monoclonal antibody is a single chain antibody.  
     
     
         42 . The reagent of  claim 35 , wherein the antibody is specific for B cell lymphomas.  
     
     
         43 . The reagent of  claim 42 , wherein the antibody is selected from the group consisting of RFB4 and LL2.  
     
     
         44 . The reagent of  claim 35 , wherein the surface marker is CD22.  
     
     
         45 . The reagent of  claim 35 , wherein the onc protein is conjugated to the antibody through recombinant fusion.  
     
     
         46 . A nucleic acid sequence encoding the reagent of  claim 35 .  
     
     
         47 . A pharmaceutical composition comprising a selective cytotoxic reagent comprising an onc protein having measurable ribonucleolytic activity covalently linked to an antibody directed against a cell surface marker specific to a B cell together with a pharmaceutically acceptable carrier.  
     
     
         48 . The pharmaceutical composition of  claim 47 , wherein the onc protein has the amino acid sequence of SEQ ID NO:1.  
     
     
         49 . The pharmaceutical composition of  claim 47 , wherein the onc protein is produced by recombinant means.  
     
     
         50 . The pharmaceutical composition of  claim 49 , wherein the onc protein has the amino acid sequence of SEQ ID NO:3.  
     
     
         51 . The pharmaceutical composition of  claim 47 , wherein the onc protein is conjugated to the antibody through recombinant means.  
     
     
         52 . The pharmaceutical composition of  claim 47 , wherein the antibody is a monoclonal antibody.  
     
     
         53 . The pharmaceutical composition of  claim 52 , wherein the monoclonal antibody is humanized.  
     
     
         54 . The pharmaceutical composition of  claim 53 , wherein the monoclonal antibody is a single chain antibody.  
     
     
         55 . The pharmaceutical composition of  claim 47 , wherein the antibody is directed against a surface marker present on B cell lymphomas.  
     
     
         56 . The pharmaceutical composition of  claim 47 , wherein the antibody is selected from the group consisting of RFB4 and LL2.