Use of vista agonists and antagonists to suppress or enhance humoral immunity

Abstract

The present invention is directed to the use of VISTA agonists alone or in association with other immune inhibitors, preferably another inhibitor of humoral immunity such as an iNOS/NO promoter or nitric oxide or a PD-1 or PD-L1 agonist or a CD40 antagonist for the treatment or prevention of conditions wherein the suppression of humoral immunity is therapeutically beneficial. The present invention is further directed to the use of VISTA antagonists alone or in association with other immune agonists, preferably another enhancer of humoral immunity such as iNOS/NO inhibitor or a PD-1 or PD-L1 antagonist or anti-CTLA-4 antibody or a CD40 agonist for the treatment or prevention of conditions wherein the enhancement of humoral immunity is therapeutically beneficial. Also, the invention relates to the use of VISTA antagonists alone or in association with another immune agonist, e.g., an iNOS/NO inhibitor or a CD40 agonist to promote the efficacy of therapeutic and prophylactic vaccines, e.g., antitumor, and antiviral vaccines.

1 - 2 . (canceled) 
     
     
         3 . A method of promoting or increasing VISTA-mediated inhibition of humoral immunity by VISTA expressing MDSCs in a subject in need thereof comprising administering a VISTA agonist selected from an agonistic VISTA antibody or a VISTA-Ig fusion protein in combination with at least one iNOS/NO promoter compound. 
     
     
         4 . The method of  claim 3 , which is used to treat a subject comprising an autoimmune, allergic, inflammatory or infectious condition wherein B cells or antibody responses are involved in disease pathology. 
     
     
         5 . A method of suppressing B cell proliferation or B cell antigen-specific antibody responses in a subject in need thereof comprising administering a VISTA agonist selected from an agonistic anti-VISTA antibody or a VISTA-Ig fusion protein in combination with at least one iNOS/NO promoter compound. 
     
     
         6 . The method of  claim 5 , which is used to treat a subject comprising an autoimmune, allergic, inflammatory or infectious condition wherein B cells or antibody responses are involved in disease pathology. 
     
     
         7 - 14 . (canceled) 
     
     
         15 . The method of  claim 3  wherein the iNOS/NO promoter is nitric oxide or a compound that comprises nitric oxide. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 5 , where the iNOS/NO promoter is a compound that promotes the synthesis of nitric oxide. 
     
     
         18 . The method of  claim 3  wherein the iNOS/NO promoter compound is an arginine derivative, NG-nitro-L-arginine methyl ester, NG-ethyl-L-arginine, N-iminoethyl-L-arginine, L-NG-methyl arginine and NG-nitro-L-arginine, NG-nitro-L-arginine methyl ester, lovastatin, a sodium salt of phenylacetic acid (NaPA), FPT inhibitor II, N-acetyl cysteine (NAC), or cAMP. 
     
     
         19 . The method of  claim 5  wherein the iNOS/NO promoter compound is an arginine derivative, NG-nitro-L-arginine methyl ester, NG-ethyl-L-arginine, N-iminoethyl-L-arginine, L-NG-methyl arginine and NG-nitro-L-arginine, NG-nitro-L-arginine methyl ester, lovastatin, a sodium salt of phenylacetic acid (NaPA), FPT inhibitor II, N-acetyl cysteine (NAC), cAMP. 
     
     
         20 . The method of claim  31  wherein the VISTA agonist is an agonistic anti-VISTA antibody. 
     
     
         21 . (canceled) 
     
     
         22 . The method of  claim 3 , wherein the VISTA agonist is a VISTA-Ig conjugate or multimeric form of VISTA. 
     
     
         23 - 32 . (canceled) 
     
     
         33 . The method of  claim 3 , which further includes the administration of a PD-1, or PD-L1 agonist or a PD-1, or PD-L1 agonist comprising an anti-PD-1 antibody or anti-PD-L1 antibody or PD-1 or PD-L1 fusion protein. 
     
     
         34 . (canceled) 
     
     
         35 . The method of  claim 5 , which further includes the administration of a PD-1, or PD-L1 agonist wherein the agonist is an anti-PD-1 antibody or anti-PD-L1 antibody or PD-1 or PD-L1 fusion protein. 
     
     
         36 - 40 . (canceled)