Treatment of psoriatic arthritis with anti-cd70 antibody

Abstract

Disclosed are CD70 binding agents, such as anti-CD70 antibodies and derivatives, that induce a cytotoxic, cytostatic or immunomodulatory without conjugation to a therapeutic agents as well as pharmaceutical compositions and kits comprising the antibody or derivative. Also disclosed are methods for the treatment of psoriatic arthritis comprising administering the CD70 binding agents to a subject.

1 . A method for the treatment of an immunological disorder in a subject comprising:
 administering to the subject an effective amount of an antibody having an antigen-binding region that specifically binds to CD70-expressing activated immune cells and at least one effector domain mediating at least an ADCC, ADCP or CDC response in the subject,   wherein:
 (a) the antibody exerts a cytostatic, cytotoxic or immunomodulatory effect on the CD70-expressing immune cells that are associated with the immunological disorder in the absence of conjugation to a therapeutic agent, 
 (b) the antibody is not conjugated to a therapeutic agent, and 
 (c) the immunological disorder is psoriatic arthritis. 
   
     
     
         2 . The method of  claim 1 , wherein the antibody depletes the CD70-expressing cells. 
     
     
         3 . The method of  claim 1 , wherein the antibody blocks binding of CD70 to CD27 receptor. 
     
     
         4 . The method of  claim 1 , wherein the CD70-expressing activated immune cells comprise activated T cells. 
     
     
         5 . The method of  claim 4 , wherein the antibody depletes the CD70-expressing activated immune cells. 
     
     
         6 . The method of  claim 5 , wherein the antibody blocks binding of CD70 to CD27 receptor. 
     
     
         7 . The method of  claim 1 , wherein the antibody is a chimeric or humanized antibody. 
     
     
         8 . The method of  claim 3 , wherein the antibody is a chimeric or humanized antibody. 
     
     
         9 . The method of  claim 8 , wherein the humanized antibody comprises an effector domain of a human IgM or IgG antibody. 
     
     
         10 . The method of  claim 9 , wherein the IgG antibody is of the human IgG1 subtype. 
     
     
         11 . The method of  claim 8 , wherein the antibody is a humanized antibody comprising a human constant region. 
     
     
         12 . The method of  claim 1 , wherein the antibody competes for binding to CD70 with an antibody comprising a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:50 and a light chain variable region having the amino acid sequence set forth in SEQ ID NO:51. 
     
     
         13 . The method of  claim 12 , wherein the antibody depletes the CD70-expressing activated immune cells. 
     
     
         14 . The method of  claim 12 , wherein the antibody is a chimeric or humanized version of a mouse antibody having a heavy chain variable region which has the amino acid sequence set forth in SEQ ID NO:50 and a light chain variable region which has the amino acid sequence set forth in SEQ ID NO:51. 
     
     
         15 . The method of  claim 12 , wherein the antibody comprises H1, H2, H3, L1, L2 and L3 complementarity-determining regions having, respectively, the amino acid sequences set forth in SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10; SEQ ID NO:16, SEQ ID NO:18, and SEQ ID NO:20. 
     
     
         16 . The method of  claim 15 , wherein the antibody is a humanized antibody. 
     
     
         17 . The method of  claim 15 , wherein the antibody is a chimeric antibody. 
     
     
         18 . The method of  claim 1 , further comprising administering a therapeutic agent. 
     
     
         19 . The method of  claim 1 , wherein the subject is human. 
     
     
         20 . The method of  claim 1 , wherein the antibody competes for binding to CD70 with an antibody comprising a heavy chain variable region having the amino acid sequence set forth in SEQ ID NO:52 and a light chain variable region having the amino acid sequence set forth in SEQ ID NO:53. 
     
     
         21 . The method of  claim 20 , wherein the antibody depletes the activated immune cells. 
     
     
         22 . The method of  claim 20 , wherein the antibody is a chimeric or humanized version of a mouse antibody having a heavy chain variable region which has the amino acid sequence set forth in SEQ ID NO:52, and the light chain variable region which has the amino acid sequence set forth in SEQ ID NO:53. 
     
     
         23 . The method of  claim 20 , wherein the antibody comprises H1, H2, and H3 complementarity determining regions having the amino acid sequences set forth in SEQ ID NO:26, SEQ ID NO:28 and SEQ ID NO:30, respectively, and further comprises L1, L2, and L3 complementarity determining regions having the amino acid sequences set forth in SEQ ID NO:36, SEQ ID NO:38 and SEQ ID NO:40, respectively. 
     
     
         24 . The method of  claim 23 , wherein the antibody is a humanized antibody.