Compositions and methods of treating disease with fgfr fusion proteins

Abstract

The invention provides FGFR fusion proteins, methods of making them, and methods of using them to treat proliferative disorders, including cancers and disorders of angiogenesis. The FGFR fusion molecules can be made in CHO cells and may comprise deletion mutations in the extracellular domains of the FGFRs which improve their stability. These fusion proteins inhibit the growth and viability of cancer cells in vitro and in vivo. The combination of the relatively high affinity of these receptors for their ligand FGFs and the demonstrated ability of these decoy receptors to inhibit tumor growth is an indication of the clinical value of the compositions and methods provided herein.

1 . (canceled) 
     
     
         2 . A method of treating mesothelioma in a human subject comprising administering an effective amount of an FGFR1 fusion protein, wherein the FGFR1 fusion protein comprises an extracellular domain of an FGFR1 polypeptide and a fusion partner, wherein the extracellular domain consists of amino acids 22 to 360 of SEQ ID NO: 130. 
     
     
         3 . The method of  claim 2 , wherein the fusion partner is an Fc polypeptide. 
     
     
         4 . The method of  claim 3 , wherein the FGFR1 fusion protein consists of amino acids 22 to 592 of SEQ ID NO: 100. 
     
     
         5 . The method of  claim 2 , further comprising administering at least one second therapeutic to the subject. 
     
     
         6 . The method of  claim 5 , wherein the at least one second therapeutic is selected from a cytostatic agent, a cytotoxic agent, an anti-angiogenic agent, and combinations thereof. 
     
     
         7 . The method of  claim 5 , wherein the at least one second therapeutic is selected from surgery, chemotherapy, radiation therapy, the administration of another biologic, and combinations thereof. 
     
     
         8 . The method of  claim 5 , wherein the at least one second therapeutic is administered before, after, or contemporaneously with the administration of the FGFR fusion protein. 
     
     
         9 . The method of  claim 4 , wherein the FGFR1 fusion protein is administered by at least one route selected from intravenously, intramuscularly, subcutaneously, topically, orally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, and intranasally. 
     
     
         10 . The method of  claim 4 , further comprising administering at least one second therapeutic to the subject. 
     
     
         11 . The method of  claim 10 , wherein the at least one second therapeutic is selected from a cytostatic agent, a cytotoxic agent, an anti-angiogenic agent, and combinations thereof. 
     
     
         12 . The method of  claim 10 , wherein the at least one second therapeutic is selected from surgery, chemotherapy, radiation therapy, the administration of another biologic, and combinations thereof. 
     
     
         13 . The method of  claim 10 , wherein the at least one second therapeutic is administered before, after, or contemporaneously with the administration of the FGFR fusion protein. 
     
     
         14 . The method of  claim 4 , wherein the FGFR1 fusion protein is administered by at least one route selected from intravenously, intramuscularly, subcutaneously, topically, orally, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intraventricularly, and intranasally.