Anti-CSF1R Antibodies for Treating PVNS

Abstract

Methods of treating pigmented villonodular synovitis (PVNS) with antibodies that bind colony stimulating factor 1 receptor (CSF1R) are provided.

1 . A method of treating a proliferative disorder involving a synovial joint and/or tendon sheath in a subject, wherein the proliferative disorder is selected from pigmented villonodular synovitis (PVNS), giant cell tumor of the tendon sheath (GCTTS), tenosynovial giant cell tumor (TGCT) such as diffuse type tenosynovial giant cell tumor (dtTGCT), and PVNS/dtTGCT, comprising administering to the subject a dose of 1-4 mg/kg of an antibody that binds human CSF1R. 
     
     
         2 . (canceled) 
     
     
         3 . A method of treating pigmented villonodular synovitis (PVNS) in a subject comprising administering to the subject a dose of 1-4 mg/kg of an antibody that binds human CSF1R. 
     
     
         4 . The method of  claim 1 , wherein the antibody is administered once per week, once per two weeks, once per three weeks, or once per month. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 3 , wherein the PVNS tumor volume is reduced by at least 30% or at least 40% or at least 50% or at least 60% or at least 70% after administration of at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten doses of the antibody that binds CSF1R. 
     
     
         7 . The method of  claim 6 , wherein the tumor volume is tumor volume in a single joint. 
     
     
         8 . The method of  claim 7 , wherein the single joint is selected from a hip joint and a knee joint. 
     
     
         9 . The method of  claim 6 , wherein the tumor volume is total tumor volume in all joints affected by PVNS. 
     
     
         10 . The method of  claim 1 , wherein, prior to administering the first dose of the antibody, the subject received a first therapy selected from surgical synovectomy, radiation beam therapy, radio isotope synovectomy, and joint replacement. 
     
     
         11 . The method of  claim 10 , wherein the disorder recurred or progressed after the first therapy. 
     
     
         12 . The method of  claim 1 , wherein the antibody is administered prior to a therapy selected from surgical synovectomy, radiation beam therapy, radio isotope synovectomy, and joint replacement, or wherein the tumor is unresectable. 
     
     
         13 . The method of  claim 1 , wherein the subject has not received prior treatment with a CSF1R inhibitor. 
     
     
         14 . The method of  claim 1 , wherein the anti-CSF1R antibody blocks binding of CSF1 and/or IL-34 to CSF1R. 
     
     
         15 . The method of  claim 1 , wherein the anti-CSF1R antibody inhibits ligand-induced CSF1R phosphorylation in vitro. 
     
     
         16 .- 39 . (canceled) 
     
     
         40 . The method of  claim 1 , wherein the subject experiences at least one of (a) a reduction in joint pain, (b) an increase range of motion in a joint, and (c) an increase in functional capacity of a joint, following at least one dose of the antibody. 
     
     
         41 . The method of  claim 1 , wherein the antibody is administered once per two weeks. 
     
     
         42 . The method of  claim 40 , wherein the antibody is administered once per two weeks. 
     
     
         43 . The method of  claim 1 , wherein the antibody is administered at a dose of 1 or 2 mg/kg once per two weeks. 
     
     
         44 . The method of  claim 40 , wherein the antibody is administered at a dose of 1 or 2 mg/kg once per two weeks. 
     
     
         45 . The method of  claim 3 , wherein the subject experiences at least one of (a) a reduction in joint pain, (b) an increase range of motion in a joint, and (c) an increase in functional capacity of a joint, following at least one dose of the antibody. 
     
     
         46 . The method of  claim 3 , wherein the antibody is administered once per two weeks. 
     
     
         47 . method of  claim 45 , wherein the antibody is administered once per two weeks. 
     
     
         48 . The method of  claim 3 , wherein the antibody is administered at a dose of 1 or 2 mg/kg once per two weeks. 
     
     
         49 . The method of  claim 45 , wherein the antibody is administered at a dose of 1 or 2 mg/kg once per two weeks. 
     
     
         50 . A method of reducing pain in a subject with pigmented villonodular synovitis (PVNS), comprising administering to the subject a dose of 1-4 mg/kg of an antibody that binds CSF1R, wherein the dose of the antibody is capable of reducing pain in PVNS subjects independently of tumor response. 
     
     
         51 . The method of  claim 50 , wherein the antibody is administered once per two weeks. 
     
     
         52 . The method of  claim 50 , wherein the antibody is administered at a dose of 1 or 2 mg/kg once per two weeks.