ErbB-2 RECEPTOR TARGETING PEPTIDE

Abstract

The ErbB-2 receptor, a member of the tyrosine kinase type 1 family of receptors, has been implicated in many human malignancies. Bacteriophage display technology was employed to identify peptides that bound to the extracellular domain of human ErbB-2. The peptide KCCYSL, most frequently occurring in the affinity selected population, was chemically synthesized and characterized for its binding activities to the recombinant extracellular domain of ErbB-2. The synthetic peptide exhibits high specificity to ErbB-2 as well as to ErbB-1, another member of ErbB family. Thus, this peptide can be employed in cancer imaging or therapeutic agent targeting to malignant cells ErbB-2 receptor.

1 .- 39 . (canceled) 
     
     
         40 . A method for diagnosing ErbB-2-positive cancer in a subject comprising:
 (a) administering to said subject the peptide-diagnostic agent complex of  claim 61 ;   (b) assessing the amount and/or localization in said subject of the diagnostic agent; and   (c) excising a tumor localized by said diagnostic agent.   
     
     
         41 . A method for treating an ErbB-2-positive cancer in a subject in need thereof comprising administering to said subject a peptide-therapeutic agent complex, wherein said peptide comprises the sequence KCCYSL. 
     
     
         42 .- 56 . (canceled) 
     
     
         57 . A method for rendering an unresectable ErbB-2-positive tumor resectable comprising administering to a subject having said tumor the peptide-therapeutic agent complex of  claim 61 . 
     
     
         58 . A method for treating metastatic ErbB-2-positive cancer comprising administering to a subject in need thereof the peptide-therapeutic agent complex of  claim 61 . 
     
     
         59 .- 60 . (canceled) 
     
     
         61 . A peptide-agent complex, wherein said peptide comprises the sequence KCCYSL. 
     
     
         62 . The complex of  claim 61 , wherein said agent is a diagnostic agent. 
     
     
         63 . The complex of  claim 62 , wherein said diagnostic agent is a radiolabel, a chemilluminescent label, a fluorescent label, a magnetic spin resonance label, or a dye. 
     
     
         64 . The complex of  claim 63 , wherein the diagnostic agent is a radiolabel selected from the group consisting of astatine 211 ,  51 chromium,  36 chlorine,  57 cobalt,  58 cobalt, copper 67 ,  152 europium, gallium 67 , iodine 123 , iodine 125 , iodine 131 , indium 111 ,  59 iron,  32 phosphorus, rhenium 186 , rhenium 188 ,  75 selenium,  35 sulphur, technicium 99m , yttrium 90 , lutetium 177 , samarium 153 , holmium 166 , bisumth 212 , bisumuth 213  and actinium 225 . 
     
     
         65 . The complex of  claim 61 , wherein said agent is a therapeutic agent. 
     
     
         66 . The complex of  claim 65 , wherein said therapeutic agent is a chemotherapeutic agent, a radiotherapeutic agent, a toxin, a cytokine or a nucleic acid construct. 
     
     
         67 . The complex of  claim 61 , wherein said peptide is between 6 and about 100 residues in length. 
     
     
         68 . The complex of  claim 67 , wherein said peptide is between 6 and about 50 residues in length. 
     
     
         69 . The complex of  claim 68 , wherein said peptide is between 6 and about 25 residues in length. 
     
     
         70 . The complex of  claim 69 , wherein said peptide is between 6 and 15 residues in length. 
     
     
         71 . A pharmaceutical composition comprising the peptide-agent complex of  claim 61 . 
     
     
         72 . The composition of  claim 71 , wherein said agent is a diagnostic agent. 
     
     
         73 . The composition of  claim 71 , wherein said agent is a therapeutic agent. 
     
     
         74 . A kit comprising the peptide-agent complex of  claim 61  in a suitable container. 
     
     
         75 . An isolated and purified peptide composition comprising a peptide comprising the sequence KCCYSL and a linker molecule coupled to said peptide, wherein said linker comprises a free reactive group. 
     
     
         76 . A method for preventing relapse of an ErbB-2-positive cancer comprising administering to a subject have been previously treated for said cancer the peptide-therapeutic agent complex of  claim 61 .