NGR receptor and methods of identifying tumor homing molecules that home to angiogenic vasculature using same

Abstract

The present invention provides a method of identifying a tumor homing molecule that homes to angiogenic vasculature by contacting a substantially purified NGR receptor with one or more molecules and determining specific binding of a molecule to the NGR receptor, where the presence of specific binding identifies the molecule as a tumor homing molecule that homes to angiogenic vasculature. The invention also provides a method of directing a moiety to angiogenic vasculature in a subject by administering to the subject a conjugate including a moiety linked to a tumor homing molecule that exhibits specific binding to an NGR receptor, whereby the moiety is directed to angiogenic vasculature. In addition, the invention provides a method of imaging the angiogenic vasculature of a tumor in a subject by administering to the subject a conjugate having a detectable moiety linked to a tumor homing molecule that exhibits specific binding to an NGR receptor and detecting the conjugate.

1 - 25 . (canceled) 
     
     
         26 . A method of inhibiting angiogenesis in a tumor of a subject, comprising administering to the subject a conjugate comprising a moiety linked to a tumor homing molecule that exhibits specific binding to an NGR receptor, whereby the moiety is directed to angiogenic vasculature. 
     
     
         27 . The method of  claim 26 , wherein said tumor homing molecule is a peptide containing the sequence NGR. 
     
     
         28 . The method of  claim 27 , wherein said moiety is a cytotoxic agent. 
     
     
         29 . The method of  claim 27 , wherein said moiety is a drug. 
     
     
         30 . The method of  claim 29 , wherein said drug is a cancer chemotherapeutic agent. 
     
     
         31 . The method of  claim 30 , wherein said cancer chemotherapeutic agent is doxorubicin. 
     
     
         32 . The method of  claim 27 , wherein said tumor homing peptide comprises a sequence selected from the group consisting of CNGRCVSGCAGRC (SEQ ID NO:3), NGRAHA (SEQ ID NO:6), CVLNGRMEC (SEQ ID NO:7), and CNGRC (SEQ ID NO:8). 
     
     
         33 . The method of  claim 32 , wherein said moiety is a cytotoxic agent. 
     
     
         34 . The method of  claim 32 , wherein said moiety is a drug. 
     
     
         35 . The method of  claim 34 , wherein said drug is a cancer chemotherapeutic agent. 
     
     
         36 . The method of  claim 35 , wherein said cancer chemotherapeutic agent is doxorubicin. 
     
     
         37 . The method of  claim 26 , wherein said tumor homing molecule is an inhibitor of a CD13-like aminopeptidase. 
     
     
         38 . The method of  claim 37 , wherein said inhibitor is selected from the group consisting of bestatin, actinonin and o-phenanthroline. 
     
     
         39 . The method of  claim 37 , wherein said moiety is a cytotoxic agent. 
     
     
         40 . The method of  claim 37 , wherein said moiety is a drug. 
     
     
         41 . The method of  claim 40 , wherein said drug is a cancer chemotherapeutic agent. 
     
     
         42 . The method of  claim 41 , wherein said cancer chemotherapeutic agent is doxorubicin. 
     
     
         43 . A method of imaging the angiogenic vasculature of a tumor in a subject, comprising:
 (a) administering to the subject a conjugate comprising a detectable moiety linked to a tumor homing molecule that exhibits specific binding to an NGR receptor,   whereby said conjugate specifically binds said angiogenic vasculature; and   (b) detecting said conjugate.   
     
     
         44 . The method of  claim 43 , wherein said detectable moiety is a radionuclide. 
     
     
         45 . The method of  claim 43 , wherein said tumor homing molecule is a peptide containing the sequence NGR. 
     
     
         46 . The method of  claim 45 , wherein said tumor homing peptide comprises a sequence selected from the group consisting of CNGRCVSGCAGRC (SEQ ID NO:3), NGRAHA (SEQ ID NO:6), CVLNGRMEC (SEQ ID NO:7), and CNGRC (SEQ ID NO:8). 
     
     
         47 . The method of  claim 46 , wherein said detectable moiety is a radionuclide. 
     
     
         48 . The method of  claim 47 , wherein said radionuclide is selected from the group consisting of indium-111, technitium-99, carbon-11 and carbon-13. 
     
     
         49 . The method of  claim 43 , wherein said tumor homing molecule is an inhibitor of a CD13-like aminopeptidase. 
     
     
         50 . The method of  claim 49 , wherein said inhibitor is selected from the group consisting of bestatin, actinonin and o-phenanthroline. 
     
     
         51 . The method of  claim 49 , wherein said detectable moiety is a radionuclide. 
     
     
         52 . The method of  claim 51 , wherein said radionuclide is selected from the group consisting of indium-1, technitium-99, carbon-11 and carbon-13. 
     
     
         53 . A substantially purified target molecule, comprising an NGR receptor that binds a peptide comprising the sequence NGR, provided that said NGR receptor does not have the amino acid sequence of CD13/aminopeptidase N (SEQ ID NO:201).