Selection of patients for combination therapy

Abstract

Described herein are methods for selecting cancer patients for treatment with a combination therapy comprising entinostat and a second therapeutic agent. In particular, methods are provided for the examination of a non-cancer cell type, myeloid-derived suppressor cells, e.g., those which are CD14-positive and HLA-DR-(lo/negative), as a therapeutic indicator in the setting of entinostat combination therapies.

1 .- 2 . (canceled) 
     
     
         3 . A method of providing a prognosis for cancer in a patient comprising:
 obtaining a peripheral blood sample from the patient, wherein the patient is diagnosed with a cancer;   measuring the number of myeloid derived suppressor cells and peripheral blood mononuclear cells in the peripheral blood sample, wherein the method further comprises   administering a combination therapy comprising entinostat and a second therapeutic agent to the patient, if the ratio of myeloid derived suppressor cells to peripheral blood mononuclear cells is between 1:200 and 1:4.   
     
     
         4 . The method of  claim 3 , wherein the peripheral blood sample is treated with an anticoagulant. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 3 , wherein measuring the number of myeloid derived suppressor cells and the peripheral blood mononuclear cells (PBMC) is performed by flow cytometry or by cytospin. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 3 , wherein the number of myeloid derived suppressor cells is identified by a cell surface marker. 
     
     
         9 . The method of  claim 8 , wherein the cell surface marker is at least one of CD11b, CD33, and CD40. 
     
     
         10 . The method of  claim 3 , wherein the number of peripheral blood mononuclear cells is identified by a cell surface marker. 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 3 , wherein the myeloid derived suppressor cell is a polymorphonuclear-MDSC or a monocytic-MDSC. 
     
     
         13 . The method of  claim 12 , wherein the polymorphonuclear-MDSC or the monocytic-MDSC is identified by a cell surface marker. 
     
     
         14 .- 17 . (canceled) 
     
     
         18 . The method of  claim 3 , wherein the ratio is selected from the group consisting of between 1:100 and 1:4, between 1:50 and 1:4, between 1:20 and 1:4, between 1:10 and 1:4, between 1:10 and 1:4, and between 1:5 and 1:4. 
     
     
         19 .- 24 . (canceled) 
     
     
         25 . The method of  claim 3 , wherein the entinostat is administered weekly or every two weeks. 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 3 , wherein the second therapeutic agent is an anti-PD-1 antibody. 
     
     
         28 .- 35 . (canceled) 
     
     
         36 . The method of  claim 3 , wherein the second therapeutic agent is exemestane. 
     
     
         37 .- 42 . (canceled) 
     
     
         43 . The method of  claim 3 , wherein the first and second binding agents each independently bind a cell surface marker. 
     
     
         44 .- 45 . (canceled) 
     
     
         46 . A method of selecting a patient for combination therapy comprising entinostat and a second therapeutic agent comprising:
 obtaining a peripheral blood sample from the patient, wherein the patient is diagnosed with a cancer;   measuring the number of cells in the peripheral blood sample which are CD14-positive and HLA-DR-(lo/negative);   measuring the number of cells in the peripheral blood sample which are CD-14 positive; and   administering the combination therapy if the ratio of the CD14-positive and HLA-DR-(lo/negative) cells to CD-14 positive cells is between 1:100 and 99:1.   
     
     
         47 . (canceled) 
     
     
         48 . A method of providing a prognosis for cancer in a patient comprising:
 obtaining a peripheral blood sample from the patient, wherein the patient is diagnosed with a cancer;   measuring the number of cells in the peripheral blood sample which are CD14-positive and HLA-DR-(lo/negative);   measuring the number of cells in the peripheral blood sample which are CD-14 positive, wherein the method further comprises,   administering a combination therapy comprising entinostat and a second therapeutic agent to the patient, if the ratio of CD14-positive and HLA-DR-(lo/negative) cells to CD-14 positive cells is between 1:100 and 99:1.   
     
     
         49 . (canceled) 
     
     
         50 . The method of  claim 48 , wherein the peripheral blood sample is treated with an anticoagulant. 
     
     
         51 . (canceled) 
     
     
         52 . The method of  claim 48 , wherein measuring number of cells in the peripheral blood sample which are CD14-positive and HLA-DR-(lo/negative) is performed by flow cytometry. 
     
     
         53 .- 64 . (canceled) 
     
     
         65 . The method of  claim 48 , wherein the entinostat is administered weekly or every two weeks. 
     
     
         66 . The method of  claim 48 , wherein the entinostat is administered every two weeks. 
     
     
         67 . The method of  claim 48 , wherein the second therapeutic agent is an anti-PD-1 antibody or an anti-PD-L1 antibody. 
     
     
         68 .- 81 . (canceled)