B-type plexin antagonists and uses thereof

Abstract

The present invention concerns the field of cancer therapy. In particular, it relates to an antagonist of a B-type plexin which prevents the interaction of the B-type plexin with ErbB-2 for use as a medicament, in particular, for treating metastasizing cancer. The present invention also contemplates a method for identifying an antagonist which prevents the interaction of a B-type plexin with ErbB-2. Finally, the invention provides for a polynucleotide encoding a B-type plexin polypeptide which lacks a functional intracellular domain and the said polypeptide.

1 .- 12 . (canceled) 
     
     
         13 . A recombinant polynucleotide encoding a B-type plexin polypeptide which lacks a functional intracellular domain. 
     
     
         14 . A polypeptide encoded by the recombinant polynucleotide of  claim 13 . 
     
     
         15 . (canceled) 
     
     
         16 . The recombinant polynucleotide of  claim 13 , wherein the B-type plexin polypeptide is a plexin B1 polypeptide which lacks a functional intracellular domain. 
     
     
         17 . The recombinant polynucleotide of  claim 13 , wherein the B-type plexin polypeptide is a human plexin B1 polypeptide which lacks a functional intracellular domain. 
     
     
         18 . The recombinant polynucleotide of  claim 13 , wherein the recombinant polynucleotide encodes amino acid residues 20-534 of human plexin B1 having the amino acid sequence set forth in SEQ ID NO. 2. 
     
     
         19 . The recombinant polynucleotide of  claim 13 , wherein the recombinant polynucleotide encodes an amino acid sequence at least 80% identical to amino acid residues 20-534 of human plexin B1 having the amino acid sequence set forth in SEQ ID NO. 2 
     
     
         20 . The recombinant polynucleotide of  claim 13 , wherein the B-type plexin polypeptide is an antagonist of a B-type plexin. 
     
     
         21 . The recombinant polynucleotide of  claim 13 , wherein the B-type plexin polypeptide prevents the interaction of a wild-type B-type plexin with ErbB-2. 
     
     
         22 . The recombinant polynucleotide of  claim 13 , wherein the B-type plexin polypeptide blocks RhoA and RhoC activation 
     
     
         23 . The recombinant polynucleotide of  claim 13  having the nucleic acid sequence set forth in SEQ ID NO: 1. 
     
     
         24 . A vector comprising the recombinant polynucleotide of  claim 13 . 
     
     
         25 . The vector of  claim 25 , wherein the vector is a plasmid, viral, retroviral vector or artificial chromosome. 
     
     
         26 . The vector of  claim 25 , wherein the vector is an expression vector. 
     
     
         27 . The vector of  claim 25 , wherein the recombinant polynucleotide encoding the B-type plexin polypeptide is operatively linked to regulatory sequences for expression of the polynucleotide in a host cell. 
     
     
         28 . A host cell comprising the recombinant polynucleotide of  claim 13 .