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 - 35 . (canceled) 
     
     
         36 . A tumor homing molecule identified 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 identifying said molecule as a tumor homing molecule, provided said molecule is not an antibody. 
     
     
         37 . A method of directing a moiety to a tumor, comprising contacting the tumor with the conjugate of claim  1 . 
     
     
         38 . The method of  claim 37 , wherein said contacting step is performed in vitro. 
     
     
         39 . The method of  claim 37 , wherein said contacting step is performed in vivo. 
     
     
         40 . A method of identifying the presence of a target molecule, which specifically binds a tumor homing molecule, wherein said tumor homing molecule is not an antibody, comprising contacting a sample of a tumor with the tumor homing molecule and detecting specific binding of said tumor homing molecule to a component of said sample, said binding identifying the presence of a target molecule. 
     
     
         41 . A method of identifying a target molecule, which is expressed in a tumor tissue, comprising the steps of: a) contacting a tumor tissue sample with a tumor homing molecule that specifically binds to said tumor tissue, wherein said tumor homing molecule is not an antibody; b) identifying in said tumor tissue sample target molecules bound by said tumor homing molecule; c) contacting a corresponding nontumor tissue sample with said tumor homing molecule; d) identifying in said corresponding nontumor tissue sample target molecules bound by said tumor homing molecule; and e) comparing said target molecules of said tumor tissue with said target molecules of said corresponding nontumor tissue, thereby identifying a target molecule expressed by said tumor tissue, wherein said target molecule specifically binds said tumor homing molecule. 
     
     
         42 . A method of obtaining a substantially isolated target molecule, which specifically binds a tumor homing molecule, comprising the step of substantially isolating the target molecule identified by the method of  claim 41 . 
     
     
         43 . A substantially isolated target molecule, which specifically binds a tumor homing molecule, obtained by the method of  claim 42 , provided said target molecule is not an integrin. 
     
     
         44 . A peptidomimetic, which competitively inhibits the binding of the target molecule of  claim 43  to a naturally occurring ligand of the target molecule. 
     
     
         45 - 68 . (canceled) 
     
     
         69 . A method of targeting in vivo a tumor containing angiogenic vasculature, comprising contacting the tumor with a molecule that selectively binds an α v -containing integrin. 
     
     
         70 . The method of  claim 69 , said molecule selected from the group of an RGD-containing peptide and an antibody that selectively binds an α v -containing integrin. 
     
     
         71 . The method of  claim 69 , wherein said α v -containing integrin is α v β 3  integrin. 
     
     
         72 . The method of  claim 69 , wherein said molecule is CDCRGDCFC (SEQ ID NO: 14).