Antagonist of the btla/hvem interaction for use in therapy

Abstract

The present invention relates to an antagonist of the BTLA/HVEM interaction for use in therapy, wherein said antagonist increases the proliferation of Vγ9Vδ2 T cells.

1 - 15 . (canceled) 
     
     
         16 . A hybridoma cell line suitable for obtaining anti-HVEM monoclonal antibodies which block the interaction between HVEM and BTLA and increase the proliferation of Vγ9Vδ2 T T cells. 
     
     
         17 . The hybridoma cell line deposited at the Collection Nationale de Cultures de Microorganismes on May 16, 2013, under the number CNCM I-4752. 
     
     
         18 . A monoclonal antibody directed against HVEM which blocks the interaction between HVEM and BTLA and increases the proliferation of Vγ9Vδ2 T T cells. 
     
     
         19 . A monoclonal antibody obtainable from the hybridoma deposited at the Collection Nationale de Cultures de Microorganismes on May 16, 2013, under the number CNCM I-4752. 
     
     
         20 . A monoclonal antibody which comprises:
 all the CDRs of the variable light chain (VL) chain of the antibody obtainable from hybridoma deposited as CNCM I-4752; and   all the CDRs pf the variable heavy chain (VH) chain of the antibody obtainable from hybridoma deposited as CNCM I-4752.   
     
     
         21 . A monoclonal antibody which comprises:
 a variable light chain (VL) comprising all the CDRs of the VL chain of the antibody obtainable from hybridoma deposited as CNCM I-4752; and   and variable heavy chain (VH) comprising all the CDRs of the VH chain of the antibody obtainable from hybridoma deposited as CNCM I-4752.   
     
     
         22 . A method of treatment comprising the administration to a subject of a therapeutically effective amount of an antagonist of the BTLA/HVEM interaction, wherein said antagonist increases the proliferation of Vγ9Vδ2 T T cells. 
     
     
         23 . A method of treatment according to  claim 22 , wherein said method is for treating a haematological malignancy, preferably a lymphoma, even more preferably a lymphoma selected among Non-Hodgkin lymphomas and Hodgkin lymphomas. 
     
     
         24 . A method of treatment according to  claim 22 , wherein said method is for treating a solid tumor, preferably a solid tumor selected in the group consisting of prostate cancer, pancreatic cancer, breast cancer, brain cancer, bladder cancer, prostate cancer, colon cancer, intestinal cancer, lung cancer, stomach cancer, cervical cancer, ovarian cancer, liver cancer, skin cancer, colorectal cancer, endometrial carcinoma, salivary gland carcinoma, kidney cancer, thyroid cancer, various types of head, neck cancer and melanoma, even more preferably selected in the group consisting of pancreatic cancer, breast cancer, prostate cancer, and melanoma. 
     
     
         25 . A method of treatment according to  claim 22 , wherein said method is for treating an autoimmune disease, preferably an autoimmune disease selected among Addison's disease, ankylosing spondylitis, aplastic anemia, autoimmune hemolytic anemia, autoimmune hepatitis, coeliac disease, Crohn's disease, dermatomyositis, Goodpasture's syndrome, Graves' disease, Guillain-Barré syndrome, Hashimoto's disease, idiopathic leucopenia, idiopathic thrombocytopenic purpura, insulin dependent diabetes mellitus (Type 1 diabetes), male infertility, mixed connective tissue disease, multiple sclerosis (MS), myasthenia gravis, pemphigoid, pemphigus vulgaris, pernicious anemia, phacogenic uveitis, primary biliary cirrhosis, primary myxoedema, Reiter's syndrome, rheumatoid arthritis (RA), scleroderma, Sjögren's syndrome, stiff man syndrome, systemic lupus erythematosus (SLE), thyrotoxicosis, ulceritive colitis, and Wegener's granulomatosis. 
     
     
         26 . A method according to  claim 22 , wherein said antagonist is chosen from antibodies directed against HVEM and fragments thereof which block the interaction between BTLA and HVEM. 
     
     
         27 . A method according to  claim 22 , wherein said antagonist is an antibody chosen among polyclonal antibodies, monoclonal antibodies, chimeric antibodies, or humanized antibodies. 
     
     
         28 . A method according to  claim 22 , wherein said antagonist is a monoclonal antibody directed against HVEM. 
     
     
         29 . A method according to  claim 22 , wherein said antagonist is a monoclonal antibody obtainable from the hybridoma deposited at the Collection Nationale de Cultures de Microorganismes on May 16, 2013, under the number CNCM I-4752. 
     
     
         30 . A method according to  claim 22 , wherein said antagonist is a fragment of an antibody directed against HVEM which block the interaction between BTLA and HVEM chosen among Fab (e.g., by papain digestion), Fab' (e.g., by pepsin digestion and partial reduction) and F(ab')2 (e.g., by pepsin digestion), facb (e.g., by plasmin digestion), pFc' (e.g., by pepsin or plasmin digestion), Fd (e.g., by pepsin digestion, partial reduction and reaggregation), Fv or scFv (e.g., by molecular biology techniques) fragments.