Binding peptides specific for the extracellular domain of ErbB2 and uses therefor

Abstract

The invention provides methods and compositions for diagnosing and treating subjects using EBPs. Specifically disclosed are peptides and peptidomimetics that bind selectively to the extracellular domain of ErbB2. These compositions are useful in the prevention and treatment of disorders characterized by ErbB2 overexpression (e.g., breast cancer).

1 . A composition comprising a peptide comprising an ErbB2 binding peptide (EBP) that binds specifically to the extracellular domain of ErbB2, wherein the ErbB2 binding peptide is between 11 and 20 amino acids in length; comprises at least two cysteines separated by 9 or 10 amino acids, and wherein the sequence of the 9 or 10 amino acids comprises the amino acid sequence set forth as STWGF (SEQ ID NO:48).  
     
     
         2 . The composition of  claim 1 , wherein the peptide comprises an amino acid sequence set forth as SEQ ID NO:1, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36.  
     
     
         3 . The composition of  claim 1 , wherein the peptide is cyclic.  
     
     
         4 . The composition of  claim 1 , wherein the peptide is conjugated to an agent.  
     
     
         5 . The composition of  claim 4 , wherein the agent is selected from the group consisting of a toxin, a radioactive molecule, a detectable label, an imaging agent, a chemotherapeutic agent, a diagnostic agent, an anti-cancer agent, an anti-angiogenic agent, an apoptosis agent, a translocating agent, and an immunomodulatory agent.  
     
     
         6 . The composition of  claim 1 , wherein the peptide is selected from the group consisting of a phage display peptide library member, a synthetic peptide library member, a combinatorial chemistry library member and a peptidomimetic.  
     
     
         7 . The composition of  claim 1 , further comprising a pharmaceutically acceptable carrier.  
     
     
         8 . The composition of  claim 1 , further comprising an anti-cancer agent.  
     
     
         9 . The composition of  claim 1 , wherein the composition is in a sustained release vehicle.  
     
     
         10 . The composition of  claim 1 , wherein the ErbB2 binding peptide inhibits phosphorylation of ErbB2.  
     
     
         11 . A method for preventing or treating a disorder characterized by ErbB2 overexpression, comprising 
 administering to a subject in need of such treatment a composition of  claim 1 , in an amount effective to inhibit the disorder.    
     
     
         12 . The method of  claim 11 , wherein the ErbB2 binding peptide comprises an amino acid sequence set forth as SEQ ID NO:1, SEQ ID NO:33, ID NO:34, SEQ ID NO:35, or SEQ ID NO:36.  
     
     
         13 . The method of  claim 11 , wherein the disorder is a cancer.  
     
     
         14 . The method of  claim 13 , wherein the cancer is a primary tumor or a metastasis.  
     
     
         15 . A method for detecting a cell characterized by ErbB2 overexpression comprising 
 contacting a composition of  claim 1  with a cell, and    determining the level of binding of the ErbB2 binding peptide to the cell,    wherein a level of binding greater than a control level is indicative of ErbB2 overexpression by the cell.    
     
     
         16 . The method of  claim 15 , wherein the ErbB2 binding peptide comprises an amino acid sequence set forth as SEQ ID NO:1, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, or SEQ ID NO:39.  
     
     
         17 . The method of  claim 15 , wherein the contacting occurs in vivo and the ErbB2 binding peptide is administered to a subject.  
     
     
         18 . The method of  claim 15 , wherein the ErbB2 binding peptide is conjugated to a detectable label.  
     
     
         19 . The method of  claim 18 , wherein the detectable label is selected from the group consisting of a radioisotope, a contrast agent, and a gaseous agent.  
     
     
         20 . The method of  claim 15 , further comprising removing the cell characterized by ErbB2 overexpression from a tissue or cell population in which it exists.