NEW USES OF ANTI-SIRPg ANTIBODIES

Abstract

The invention pertains to the field of immunotherapy. The present invention provides new uses of anti-SIRPg antibodies for the treatment and/or the prevention of autoimmune disorders or diseases.

1 . A human anti-SIRPg antibody or antigen-binding fragment thereof or antigen binding antibody mimetic for its use in the prevention and/or the treatment of a disease or a disorder, in particular a human disease or a human disorder, in which T cell proliferation has a deleterious effect, wherein said anti-SIRPg antibody or antigen-binding fragment thereof or antigen binding antibody mimetic inhibits the binding of human CD47 to human SIRPg,
 the disease or disorder in which T cell proliferation has a deleterious effect being selected from the group consisting of:
 an auto-immune disease, 
 a chronic inflammatory disease, 
 a chronic neuroinflammatory disease, 
 an immune-metabolic disease, 
 a cardiovascular disease caused by a systemic inflammation, and 
 transplant dysfunction. 
   
     
     
         2 . The human anti-SIRPg antibody or antigen-binding fragment thereof or antigen binding antibody mimetic for use according to  claim 1 , wherein said antibody or antigen-binding fragment thereof decreases or inhibits the proliferation of T cells as compared with a negative control. 
     
     
         3 . The human anti-SIRPg antibody or antigen-binding fragment thereof or antigen binding antibody mimetic for use according to  claim 1 , wherein said disease is selected from the group consisting of:
 an auto-immune disease, and   a chronic inflammatory disease.   
     
     
         4 . The human anti-SIRPg antibody or antigen-binding fragment thereof or antigen binding antibody mimetic for use according to  claim 1 , wherein said disorder is a transplant dysfunction. 
     
     
         5 . The human anti-SIRPg antibody or antigen-binding fragment thereof or antigen binding antibody mimetic for use according to  claim 1 , wherein said anti-SIRPg antibody or antigen-binding fragment thereof specifically binds to human SIRPa. 
     
     
         6 . The human anti-SIRPg antibody or antigen-binding fragment thereof or antigen binding antibody mimetic for use according to  claim 5 , wherein said anti-SIRPg antibody or antigen-binding fragment thereof or antigen binding antibody mimetic decreases the binding of human CD47 to human SIRPa. 
     
     
         7 . The human anti-SIRPg antibody or antigen-binding fragment thereof or antigen binding antibody mimetic for use according to  claim 1 , wherein the antibody or antigen-binding fragment thereof or antigen binding antibody mimetic has a variable heavy chain comprising the CDRs comprising or consisting of the amino acid sequence of SEQ ID No: 2, SEQ ID No: 3 and SEQ ID No: 4; and a variable light chain comprising the CDRs comprising or consisting of the amino acid sequence of SEQ ID No: 6, SEQ ID No: 8 and SEQ ID No: 7, in particular the variable heavy light chain comprises the amino acid sequence of SEQ ID No: 1 and the variable light chain comprises the amino acid sequence of SEQ ID No: 5; more particularly the antibody is Kwar23. 
     
     
         8 . The human anti-SIRPg antibody or antigen-binding fragment thereof or antigen binding antibody mimetic for use according to  claim 1 , wherein said anti-SIRPg antibody or antigen-binding fragment thereof or antigen binding antibody mimetic does not specifically bind to human SIRPa. 
     
     
         9 . The human anti-SIRPg antibody or antigen-binding fragment thereof or antigen binding antibody mimetic for use according to  claim 8 , wherein said anti-SIRPg antibody or antigen-binding fragment thereof or antigen binding antibody mimetic increases the binding of human CD47 to human SIRPa. 
     
     
         10 . A combination product comprising:
 at least one anti-human SIRPg antibody or antigen-binding fragment thereof or antigen-binding antibody mimetic for use as defined in  claim 1 , and   at least one second therapeutic agent selected from the group consisting of immunotherapeutic agents, immunosuppressive agents, antibiotics and probiotics.   for simultaneous, separate or sequential use as a medicament.   
     
     
         11 . The combination product for its use according to  claim 10 , wherein said immunosuppressive agent is selected from the group consisting of Cyclosporine A, tacrolimus, mycophenolate mofetil, rapamycine, steroids, anti-TNF agents, anti-IL-23 agents. 
     
     
         12 . An in vitro or ex vivo method to determine a SIRPg positive cells in a subject from a biological sample of said subject, comprising:
 i) determining in vitro the expression and/or the level of expression of SIRPg, in a biological sample of said subject using the anti-human SIRPg antibody or antigen-binding fragment thereof or antigen-binding antibody mimetic as defined in any one of  claims 1  to  9 , in particular the antibody or antigen-binding fragment or antigen binding antibody mimetic thereof as defined in  claim 8 .   
     
     
         13 . Use of at least one anti-human SIRPg antibody or antigen-binding fragment thereof or antigen-binding antibody mimetic as defined in  claim 1 , in an in vitro or ex vivo method wherein SIRPg is used as a biomarker that is predictive for the response to a treatment in a subject. 
     
     
         14 . An in vitro method of predicting the response of a subject to a treatment, in particular with an anti-human SIRPg antibody or antigen-binding fragment thereof or antigen-binding antibody mimetic as defined in  claim 1 , comprising:
 determining the expression level of SIRPg in a sample previously obtained from a subject, in particular a human subject, in particular with an anti-human SIRPg antibody or antigen-binding fragment thereof or antigen-binding antibody mimetic as defined in  claim 1 , and   comparing the expression level of SIRPg to a value representative of an expression level of SIRPg in a non-responding subject population,   wherein a higher expression level of SIRPg in the sample of the subject is indicative for a subject who will respond to the treatment.