Specific human antibodies for selective cancer therapy

Abstract

The present invention is directed to a peptide or polypeptide comprising an Fv molecule, a construct thereof, a fragment of either, or a construct of a fragment having enhanced binding characteristics so as to bind selectively and/or specifically to a target cell in favor of other cells, wherein the binding selectivity or specificity is primarily determined by a first hypervariable region, and wherein the Fv is a scFv or a dsFv, and optionally having one or more tags. The enhanced binding is directed to a substantially exposed and/or over-expressed binding site on or in a target comprising a cell in favor of other cells on or in which the binding site is not substantially available and/or expressed. The invention is further directed to a method for isolating such peptides and polypeptides from a phage display library and to the nucleic acid molecules encoding them. The invention provides for a pharmaceutical composition comprising the peptide or polypeptide and kits for diagnosis and treatment of disease, specifically cancer, most specifically acute myeloid leukemia.

1 . A peptide or polypeptide or a fragment thereof comprising an Fv molecule, wherein said Fv molecule comprises a heavy chain variable region and a light chain variable region, and 
 wherein the Fv is a scFv or a dsFv, and optionally having one or more tags, and    wherein the heavy chain variable region comprises CDR3, CDR2 and CDR1 regions comprising the amino acid sequences SEQ ID NOS:19, 115 and 114, respectively; and    wherein the Fv molecule is capable of binding one or more cell types selected from the group consisting of leukemia cells and cells expressing glycocalicin.    
     
     
         2 . The peptide or polypeptide of  claim 1 , wherein the heavy chain variable region comprises CDR3, CDR2 and CDR1 regions consisting of the amino acid sequences SEQ ID NOS:19, 115 and 114, respectively.  
     
     
         3 . The peptide or polypeptide of  claim 1 , wherein the CDR3 region consists of SEQ ID NO:19.  
     
     
         4 . The peptide or polypeptide of  claim 1 , wherein the CDR2 region consists of SEQ ID NO:115.  
     
     
         5 . The peptide or polypeptide of  claim 1 , wherein the CDR1 region consists of SEQ ID NO:114.  
     
     
         6 . The peptide or polypeptide of  claim 1 , wherein the leukemia cells are selected from the group consisting of B lineage leukemia cells, T lineage leukemia cells, and myeloid lineage leukemia cells.  
     
     
         7 . The peptide or polypeptide of  claim 6 , wherein the B lineage leukemia cells are selected from the group consisting of B-CLL and B-ALL.  
     
     
         8 . The peptide or polypeptide of  claim 6 , wherein the myeloid lineage leukemic cells are selected from the group consisting of CML and AML.  
     
     
         9 . The peptide or polypeptide of  claim 1 , wherein the cells expressing glycocalicin are platelets.