Dna hypomethylating agents for cancer therapy

Abstract

The present invention relates to a method of treating and/or preventing cancer comprising administering a combination of an effective amount of a DNA hypomethylating agent and an effective amount of at least one immunomodulatory agent and/or optionally an effective amount of at least one targeted therapy agent.

1 . A method of treating cancer in a patient in need thereof, the method comprising administering to the patient an effective amount of a DNA hypomethylating agent and an effective amount of at least one immunomodulatory agent, wherein the immunomodulatory agent is selected from the group consisting of a cancer vaccine, a therapeutic cytokine, and a cellular therapy. 
     
     
         2 . The method of  claim 1 , wherein the DNA hypomethylating agent is selected from the group consisting of 5-azacytidine, 5-aza-2′-deoxycytidine (5-AZA-CdR), zebularine, procainamide, procaine, hydralazine, epigallocathechin-3-gallate, RG108, and MG98. 
     
     
         3 . The method of  claim 1 , further comprising administering an immunomodulating antibody. 
     
     
         4 . The method of  claim 3 , wherein the immunomodulating antibody is selected from the group consisting of an anti-CTLA-4, an anti-PDL-1, an anti-PDL-2, an anti-PD1, an anti-CD137, an anti-CD40 and an anti-OX-40 antibody. 
     
     
         5 . The method of  claim 1 , wherein the immunomodulatory agent is the cancer vaccine and the cancer vaccine is selected from the group consisting of anti-idiotypic antibodies, inhibitors of angiogenesis, tumor antigen specific peptides and recombinant proteins. 
     
     
         6 . The method of  claim 1 , wherein the immunomodulatory agent is the therapeutic cytokine and the therapeutic cytokine is selected from the group consisting of GM-CSF, IL-2, IL-12, TNF-α, IFN γ and IFN-α. 
     
     
         7 . The method according to  claim 1 , wherein the immunomodulatory agent is cellular therapy and the cellular therapy is the administration of a cell selected from the group consisting of T cells; stem cells; dendritic cells; gene-modified or pharmacologically-modified immune cells; and gene-modified or pharmacologically-modified cancer cells. 
     
     
         8 . The method of  claim 1 , wherein the cancer is caused by a solid or hematopoietic tumor. 
     
     
         9 . The method of  claim 8 , wherein the tumor is resistant or refractory to at least one anti-tumor therapy. 
     
     
         10 . The method of  claim 1 , wherein the DNA hypomethylating agent and the immunomodulatory agent are administered simultaneously or sequentially. 
     
     
         11 . The method according to  claim 1 , further comprising administering an effective amount of at least one targeted therapy agent to the patient in need thereof. 
     
     
         12 . The method of  claim 11 , wherein the targeted therapy agent is a MAP kinase pathway inhibitor or a WNT pathway inhibitor. 
     
     
         13 . The method of  claim 12 , wherein the targeted therapy agent is the MAP kinase pathway inhibitor, and the MAP kinase pathway inhibitor is selected from the group consisting of a BRAF inhibitor, a MEK inhibitor, a PI3K inhibitor and a c-KIT inhibitor. 
     
     
         14 . The method of  claim 13 , wherein the MAP kinase pathway inhibitor is the BRAF inhibitor, and the BRAF inhibitor is selected from the group consisting of GDC-0879, PLX-4720, Sorafenib Tosylate, dabrafenib and LGX818. 
     
     
         15 . The method of  claim 13 , wherein the MAP kinase pathway inhibitor is the MEK inhibitor, and the MEK inhibitor is selected from the group consisting of GSK1120212, selumetinib and MEK162. 
     
     
         16 . The method of  claim 12 , wherein the targeted therapy agent is the WNT pathway inhibitor, and the WNT pathway inhibitor is a beta catenin inhibitor or a frizzled inhibitor. 
     
     
         17 . The method of  claim 16 , wherein the WNT pathway inhibitor is the beta catenin inhibitor, and the beta catenin inhibitor is selected from the group consisting of niclosamide, XAV-939, FH 535 and ICG 001. 
     
     
         18 . The method of  claim 3 , wherein the cancer is caused by a solid or hematopoietic tumor. 
     
     
         19 . The method of  claim 18 , wherein the tumor is resistant or refractory to at least one anti-tumor therapy. 
     
     
         20 . The method of  claim 3 , wherein the DNA hypomethylating agent, the immunomodulatory agent and the immunomodulating antibody are administered simultaneously or sequentially. 
     
     
         21 . A method of preventing cancer in a patient in need thereof, the method comprising administering to the patient an effective amount of a DNA hypomethylating agent and an effective amount of at least one immunomodulatory agent, wherein the immunomodulatory agent is selected from the group consisting of an immunomodulatory antibody, a cancer vaccine, a therapeutic cytokine, and a cellular therapy.