Method for treating cancer

Abstract

The present invention provides a method for treating or alleviating a symptom of a disorder, e.g., immune evasion, cancer-cell induced immune dysfunction, reduced immune response, lowered inflammation, decreased expression of a major histocompatibility complex (MHC), or cancer, characterized by aberrant, misregulated, or increased Enhancer of Zeste Homolog 2 (EZH2) activity in a cell or subject in need thereof by contacting the cell or administering to the subject a therapeutically effective amount of an EZH2 inhibitor.

1 .- 2 . (canceled) 
     
     
         3 . A method for boosting an immune response in a subject in need thereof comprising a step of administering to the subject a therapeutically effective amount of an EZH2 inhibitor. 
     
     
         4 . (canceled) 
     
     
         5 . A method for increasing inflammation in a subject in need thereof comprising a step of administering to the subject a therapeutically effective amount of an EZH2 inhibitor. 
     
     
         6 . A method for treating a cancer or a cell proliferative disorder in a subject in need thereof comprising a step of administering to the subject a therapeutically effective amount of an EZH2 inhibitor. 
     
     
         7 .- 9 . (canceled) 
     
     
         10 . The method of  claim 3 , wherein the subject has aberrant, misregulated, or increased EZH2 activity. 
     
     
         11 . The method of  claim 3 , wherein the subject has a chromosomal translocation t(x;18)(p11.2;q11.2). 
     
     
         12 . The method of  claim 11 , wherein the translocation causes a SS18-SSX fusion gene. 
     
     
         13 . The method of  claim 3 , wherein the subject has reduced function or expression of INI1. 
     
     
         14 . The method of  claim 13 , wherein the subject has reduced function and expression of INI1. 
     
     
         15 . The method of  claim 3 , wherein the EZH2 inhibitor is Compound A, having the following formula: 
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof. 
     
     
         16 . The method of  claim 3 , wherein the EZH2 inhibitor is selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof. 
     
     
         17 . The method of  claim 3 , wherein the method further comprises administering an additional therapeutic agent, wherein the additional therapeutic agent is a chemotherapeutic compound. 
     
     
         18 . The method of  claim 17 , wherein the chemotherapeutic compound is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor. 
     
     
         19 . (canceled) 
     
     
         20 . The method of  claim 3 , wherein the subject is a human. 
     
     
         21 . The method of  claim 3 , wherein the immune response in need of boosting is characterized by reduced expression of one or more of MHC, P2 microglobulin, Tumor Necrosis Factor (TNF) receptor, Low Molecular Mass Polypeptide 2 (LMP2), Low Molecular Mass Polypeptide 7 (LMP7), Transporter Associated with Antigen Processing (TAP), and TAP-associated glycoprotein (tapasin). 
     
     
         22 . The method of  claim 21 , wherein the MHC is human leukocyte antigen (HLA), wherein the HLA is selected from the group consisting of HLA-A, HLA B, HLA-C, HLA DM alpha, HLA DM beta, HLA-DO alpha, HLA DO beta 1, HLA DP alpha 1, HLA DP beta 1, HLA DR alpha, HLA-DR beta 1, HLA-DR beta 3, HLA DR beta 4, HLA E, HLA F, HLA G, HLA K, and HLA L. 
     
     
         23 . The method of  claim 6 , wherein the cancer is characterized by reduced expression of one or more of MHC, P2 microglobulin, Tumor Necrosis Factor (TNF) receptor, Low Molecular Mass Polypeptide 2 (LMP2), Low Molecular Mass Polypeptide 7 (LMP7), Transporter Associated with Antigen Processing (TAP), and TAP-associated glycoprotein (tapasin). 
     
     
         24 . The method of  claim 23 , wherein the MHC is human leukocyte antigen (HLA), wherein the HLA is selected from the group consisting of HLA-A, HLA B, HLA-C, HLA DM alpha, HLA DM beta, HLA-DO alpha, HLA DO beta 1, HLA DP alpha 1, HLA DP beta 1, HLA DR alpha, HLA-DR beta 1, HLA-DR beta 3, HLA DR beta 4, HLA E, HLA F, HLA G, HLA K, and HLA L. 
     
     
         25 . The method of  claim 6 , wherein the EZH2 inhibitor is Compound A, having the following formula: 
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof. 
     
     
         26 . The method of  claim 6 , wherein the method further comprises administering an additional therapeutic agent, wherein the additional therapeutic agent is a chemotherapeutic compound. 
     
     
         27 . The method of  claim 26 , wherein the chemotherapeutic compound is selected from the group consisting of a PD-1 inhibitor, a PD-L1 inhibitor, and a CTLA-4 inhibitor.