Tumor homing molecules, conjugates derived therefrom, and methods of using same

Abstract

The present invention provides tumor homing molecules, which selectively home to a tumor. The invention also provides methods of using a tumor homing molecule to target an agent such as a drug to a selected tumor or to identify the target molecule expressed by the tumor. The invention also provides methods of targeting a tumor containing angiogenic vasculature by contacting the tumor with a molecule that specifically binds an α v -containing integrin. The invention further provides molecules that can selectively home to angiogenic vasculature. In addition, the invention provides a target molecule, which is specifically bound by a tumor homing molecule and is expressed by angiogenic vasculature. The invention also provides antibodies that bind to the target molecule and peptidomimetics that competitively inhibit binding of a ligand to the target molecule.

1 - 15 . (canceled) 
     
     
         15 . A conjugate, comprising a tumor homing molecule linked to a moiety, said tumor homing molecule obtained by in vivo panning, comprising the steps of: a) administering to a first subject having a tumor a library of diverse molecules; b) collecting a sample of the tumor; c) identifying a molecule that homes to said tumor; d) collecting a sample of normal tissue corresponding to said tumor; and e) determining that said molecule that homes to said tumor is not present in said normal tissue, thereby obtaining said tumor homing molecule, provided said tumor homing molecule is not an antibody. 
     
     
         16 . The conjugate of  claim 15 , wherein said molecule is a nucleic acid molecule. 
     
     
         17 . The conjugate of  claim 15 , wherein said molecule is a peptidomimetic. 
     
     
         18 - 28 . (canceled) 
     
     
         29 . A tumor homing peptide identified by in vivo panning, comprising the steps of: a) administering to a first subject having a tumor a library of diverse peptides; b) collecting a sample of the tumor; c) identifying a peptide that homes to said tumor; d) collecting a sample of normal tissue corresponding to said tumor; and e) determining that said peptide that homes to said tumor is not present in said normal tissue, thereby identifying said peptide as a tumor homing peptide, provided said peptide is not an antibody. 
     
     
         30 . The tumor homing peptide of  claim 29 , wherein said sample of normal tissue corresponding to said tumor is collected from said first subject. 
     
     
         31 . The tumor homing peptide of  claim 29 , wherein said sample of normal tissue corresponding to said tumor is collected from a second subject. 
     
     
         32 . The tumor homing peptide of  claim 29 , wherein said tumor is a breast tumor. 
     
     
         33 . The tumor homing peptide of  claim 29 , wherein said tumor is a melanoma. 
     
     
         34 . The tumor homing peptide of  claim 29 , wherein said tumor is a Kaposi's sarcoma. 
     
     
         35 . A tumor homing peptide selected from the group consisting of CLSGSLSC (SEQ ID NO: 4) and CGSLVRC (SEQ ID NO: 5). 
     
     
         36 - 44 . (canceled) 
     
     
         45 . A molecule, which specifically binds to the target molecule of claim  43 . 
     
     
         46 . A molecule, which competitively inhibits the binding of the target molecule of claim  43  to the tumor homing molecule. 
     
     
         47 . The molecule of  claim 46 , which is a peptide. 
     
     
         48 . The peptide of  claim 47 , which contains the amino acid sequence NGR. 
     
     
         49 . The peptide of  claim 48 , which has the amino acid sequence CNGRCVSGCAGRC (SEQ ID NO: 3). 
     
     
         50 . The peptide of  claim 47 , which contains the amino acid sequence GSL. 
     
     
         51 . The peptide of  claim 50 , which has the amino acid sequence CGSLVRC (SEQ ID NO: 5). 
     
     
         52 . A target molecule, which is expressed in tumor vasculature, wherein said target molecule binds CNGRC (SEQ ID NO: 8) with a higher affinity than said target molecule binds CDCRGDCFC (SEQ ID NO: 1). 
     
     
         53 . An antibody that specifically binds the target molecule of claim  43 . 
     
     
         54 . The antibody of  claim 53 , which is a monoclonal antibody. 
     
     
         55 - 72 . (canceled)