Anti-human vista antibodies and use thereof

Abstract

The invention provides antagonistic and agonistic anti-human VISTA antibodies and antibody fragments. These antagonist antibodies and antibody fragments may be used to inhibit or block VISTA's suppressive effects on T cell immunity and thereby promote T cell immunity. These agonist antibodies and antibody fragments may be used to potentiate or enhance or mimic VISTA's suppressive effects on T cell immunity and thereby suppress T cell immunity. These antagonist antibodies and antibody fragments are especially useful in the treatment of cancer and infectious conditions. These agonist antibodies and antibody fragments are especially useful in the treatment of autoimmunity, allergy, inflammatory conditions, GVHD, sepsis and transplant recipients. Screening assays for identifying these agonists are also provided.

1 - 52 . (canceled) 
     
     
         53 . A method of suppressing T cell immunity in a subject in need thereof comprising administering an effective amount of an agonistic antibody comprising an antigen binding region that specifically binds to human V-domain Ig Suppressor of T cell Activation (human VISTA), wherein (i) the antibody or antibody fragment agonizes or promotes the suppressive effect of VISTA on T cell immunity, wherein said antibody is selected from the following:
 (i) one comprising a heavy chain comprising the V H  CDRs of SEQ ID NO:200, 201 and 202 and comprising a light chain comprising the VL CDRs of SEQ ID NO:203, 204 and 205;   (ii) one comprising a heavy chain comprising the V H  CDRs of SEQ ID NO:380, 381 and 382 and comprising a light chain comprising the VL CDRs of SEQ ID NO:383, 384 and 385;   (iii) one comprising a heavy chain comprising the V H  CDRs of SEQ ID NO:470, 471 and 472 and comprising a light chain comprising the VL CDRs of SEQ ID NO:473, 474 and 475;   (iv) one comprising a heavy chain comprising the V H  CDRs of SEQ ID NO:500, 501 and 502 and the VL CDR polypeptides of SEQ ID NO:503, 504 and 505;   and wherein the antibody of any of (i) to (iv) comprises a human IgG2 constant or Fc region.   
     
     
         54 . The method of  claim 53 , wherein:
 for embodiment (i) the antibody comprises the VH polypeptide of SEQ ID NO:206 and the VL polypeptide of SEQ ID NO:208;   for embodiment (ii) the antibody comprises the VH polypeptide of SEQ ID NO:386 and the VL polypeptide of SEQ ID NO:388;   for embodiment (iii) the antibody comprises the VH polypeptide of SEQ ID NO:476 and the VL polypeptide of SEQ ID NO:478; or   for embodiment (iv) the antibody comprises the VH polypeptide of SEQ ID NO:506 and the VL polypeptide of SEQ ID NO:508.   
     
     
         55 . The method of  claim 53 , wherein the subject has an autoimmune disease involving T cells. 
     
     
         56 . The method of  claim 54 , wherein the subject has an autoimmune disease involving T cells. 
     
     
         57 . The method of  claim 53 , wherein the subject has an inflammatory disease involving T cells. 
     
     
         58 . The method of  claim 54 , wherein the subject has an inflammatory disease involving T cells. 
     
     
         59 . The method of  claim 53 , wherein the subject has an allergic disease involving T cells. 
     
     
         60 . The method of  claim 54 , wherein the subject has an allergic disease involving T cells. 
     
     
         61 . The method of  claim 53 , wherein the human IgG2 constant or Fc region binds to Fc gamma receptors including human CD32A. 
     
     
         62 . The method of  claim 54 , wherein the human IgG2 constant or Fc region binds to Fc gamma receptors including human CD32A. 
     
     
         63 . The method of  claim 53 , wherein the agonist antibody is chimeric, human or humanized. 
     
     
         64 . The method of  claim 55 , wherein the agonist antibody is chimeric, human or humanized. 
     
     
         65 . The method of  claim 57 , wherein the agonist antibody is chimeric, human or humanized. 
     
     
         66 . The method of  claim 59 , wherein the agonist antibody is chimeric, human or humanized. 
     
     
         67 . The method of  claim 53 , which includes the administration of another immunosuppressant. 
     
     
         68 . The method of  claim 53 , which includes the administration of another immunosuppressant.