Anti-cd134 (ox40) antibodies and uses thereof

Abstract

The invention provides antibodies that specifically bind to human CD134. Invention anti-human CD134 antibodies specifically bind to the extracellular domain of human CD134, including non-OX40 ligand (OX40L) binding domains on human CD134, which is expressed on e.g. activated human conventional effector CD4 and/or CD8 T lymphocytes (Teffs) and on activated human suppressive regulatory CD4 lymphocytes (Tregs). Invention anti-human CD134 antibodies are useful (e.g. to empower Teffs anti-cancer effector function and/or to inhibit Tregs suppressive function) for cancer treatment.

1 - 40 . (canceled) 
     
     
         41 . A method of enhancing an immune response in a human subject, comprising administering to the human subject a therapeutically effective amount of an antibody that binds human or CD134, or an antigen binding fragment thereof, comprising a heavy chain variable region comprising:
 (a) a CDR1 comprising the amino acid sequence of SEQ ID NO:6;   (b) a CDR2 comprising the amino acid sequence of SEQ ID NO:7   (c) a CDR3 comprising the amino acid sequence of SEQ ID NO:8, and a light chain variable region comprising:   (a) a CDR1 comprising the amino acid sequence of SEQ ID NO:9;   (b) a CDR2 comprising the amino acid sequence of SEQ ID NO:10   (c) a CDR3 comprising the amino acid sequence of SEQ ID NO:11.   
     
     
         42 . A method according to  claim 41  wherein the enhanced immune response comprises an increase in the immunostimulator/effector function of T-effector cells, optionally as a result of proliferation of those cells, and/or a down-regulation of the immunosuppressor function of T-regulatory cells, optionally without expansion in numbers of those cells. 
     
     
         43 . A method of treating cancer in a human subject in need thereof, comprising administering to the human subject a therapeutically effective amount of an antibody that binds human CD134, or an antigen binding fragment thereof, comprising a heavy chain variable region comprising:
 (a) a CDR1 comprising the amino acid sequence of SEQ ID NO:6;   (b) a CDR2 comprising the amino acid sequence of SEQ ID NO:7   (c) a CDR3 comprising the amino acid sequence of SEQ ID NO:8, and a light chain variable region comprising:   (a) a CDR1 comprising the amino acid sequence of SEQ ID NO:9;   (b) a CDR2 comprising the amino acid sequence of SEQ ID NO:10   (c) a CDR3 comprising the amino acid sequence of SEQ ID NO:11.   
     
     
         44 . A method according to  claim 43 , wherein the cancer is selected from the group consisting of lung cancer, prostate cancer, breast cancer, head and neck cancer, oesophageal cancer, stomach cancer, colon cancer, colorectal cancer, bladder cancer, cervical cancer, uterine cancer, ovarian cancer, liver cancer, hematological cancer, or any disease or disorder characterized by uncontrolled cell growth. 
     
     
         45 . A method of reducing the size of a tumour or inhibiting the growth of cancer cells in a subject or reducing or inhibiting the development of metastatic cancer in an subject suffering from cancer, comprising administering to the human subject an antibody that binds human CD134, or an antigen binding fragment thereof, comprising a heavy chain variable region comprising:
 (a) a CDR1 comprising the amino acid sequence of SEQ ID NO:6;   (b) a CDR2 comprising the amino acid sequence of SEQ ID NO:7   (c) a CDR3 comprising the amino acid sequence of SEQ ID NO:8, and a light chain variable region comprising:   (a) a CDR1 comprising the amino acid sequence of SEQ ID NO:9;   (b) a CDR2 comprising the amino acid sequence of SEQ ID NO:10   (c) a CDR3 comprising the amino acid sequence of SEQ ID NO:11.   
     
     
         46 - 48 . (canceled) 
     
     
         49 . The method of  claim 41 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:4 or a variant of that sequence having 1, 2 or 3 amino acid substitutions in the framework regions; and/or a light chain variable region comprising the amino acid sequence of SEQ ID NO:5 or a variant of that sequence having 1, 2 or 3 amino acid substitutions in the framework regions. 
     
     
         50 . The method of  claim 41 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:4 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:5. 
     
     
         51 . The method of  claim 41 , wherein the antibody is a human antibody. 
     
     
         52 . The method of  claim 41 , wherein the antibody or antigen binding fragment thereof is a chimeric, humanized, or deimmunized antibody. 
     
     
         53 . The method of  claim 43 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:4 or a variant of that sequence having 1, 2 or 3 amino acid substitutions in the framework regions; and/or a light chain variable region comprising the amino acid sequence of SEQ ID NO:5 or a variant of that sequence having 1, 2 or 3 amino acid substitutions in the framework regions. 
     
     
         54 . The method of  claim 43 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:4 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:5. 
     
     
         55 . The method of  claim 43 , wherein the antibody is a human antibody. 
     
     
         56 . The method of  claim 43 , wherein the antibody or antigen binding fragment thereof is a chimeric, humanized, or deimmunized antibody. 
     
     
         57 . The method of  claim 41 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:4 or a variant of that sequence having 1, 2 or 3 amino acid substitutions in the framework regions; and/or a light chain variable region comprising the amino acid sequence of SEQ ID NO:5 or a variant of that sequence having 1, 2 or 3 amino acid substitutions in the framework regions. 
     
     
         58 . The method of  claim 45 , wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:4 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:5. 
     
     
         59 . The method of  claim 45 , wherein the antibody is a human antibody. 
     
     
         60 . The method of  claim 45 , wherein the antibody or antigen binding fragment thereof is a chimeric, humanized, or deimmunized antibody.