Flt4 (vegfr-3) as a target for tumor imaging and anti-tumor therapy

Abstract

The present invention provide purified Flt4 receptor tyrosine kinase polypeptides and fragments thereof, polynucleotides encoding such polypeptides, antibodies that specifically bind such polypeptides, and uses therefor.

1 - 42 . (canceled) 
     
     
         43 . A method of inhibiting genesis of blood vessels in a mammalian organism having a disease characterized by expression of Flt4 tyrosine kinase (Flt4) in blood vessels, the method comprising administering to said mammalian organism a composition, said composition comprising a polynucleotide comprising a nucleotide sequence that encodes an inhibitor of the binding of an Flt4 ligand protein to Flt4 expressed in cells of said organism,
 wherein the inhibitor comprises a soluble polypeptide comprising an extracellular domain fragment of Flt4 set forth in SEQ ID NO: 2 or SEQ ID NO: 4, wherein the polypeptide and the fragment are capable of binding to human VEGF-C(SEQ ID NO: 21), and   wherein the polynucleotide is administered in an amount effective to inhibit Flt4-mediated proliferation of said blood vessels in the organism.   
     
     
         44 . The method according to  claim 43  wherein said mammalian organism is human. 
     
     
         45 . The method according to  claim 44 , wherein the human has a tumor characterized by blood vessels that express Flt4. 
     
     
         46 . The method according to  claim 44 , wherein the composition comprises an expression vector that comprises the polynucleotide operably linked to one or more expression control sequences. 
     
     
         47 . The method according to  claim 46 , wherein the polynucleotide is operably linked to a promoter to promote expression in cells of the mammalian organism. 
     
     
         48 . The method according to  claim 47 , wherein the polynucleotide that encodes the soluble polypeptide that comprises the fragment of Flt4 is a cDNA.