Methods of enhancing antibody-dependent cellular cytotoxicity

Abstract

The application relates to method of increasing antibody-dependent cellular cytotoxicity in a subject receiving therapeutic monoclonal antibody treatment. In some embodiments, methods are provided for administering to subject to a subject in need thereof a therapeutic antibody in conjunction with an ADCC enhancer molecule.

What is claimed is: 
     
         1 . A method of increasing antibody-dependent cellular cytotoxicity (ADCC) in a subject receiving therapeutic antibody treatment, the method comprising administering to the subject an ADCC enhancer molecule and a therapeutic antibody, wherein the ADCC enhancer molecule is in an amount sufficient to increase ADCC and the ADCC enhancer molecule is 2-amino-8-[4-(pyrrolidinylcarbonyl)phenyl]-(3H-benzo [f] azepin-4-yl)}-N,N-dipropylcarboxamide represented by the structure: 
       
         
           
           
               
               
           
         
         and wherein the amount sufficient to increase ADCC is between 0.1 mg/m 2  and 10 mg/m 2 . 
       
     
     
         2 . The method of  claim 1 , wherein the therapeutic monoclonal antibody is a therapeutic anti-CD20 monoclonal antibody, a therapeutic anti-Her2 monoclonal antibody, or a therapeutic anti-EGFR monoclonal antibody. 
     
     
         3 . The method of  claim 1 , wherein therapeutic antibody is selected from the group consisting of rituximab, trastuzumab, cetuximab, and panitumumab. 
     
     
         4 . The method of  claim 1 , further comprising administering to the subject a therapeutically effective amount of one or more chemotherapeutic agents. 
     
     
         5 . The method of  claim 1 , wherein the subject has an FcγR polymorphism. 
     
     
         6 . The method of  claim 1 , wherein the subject has a KRAS mutation. 
     
     
         7 . The method of  claim 1 , wherein the subject has previously been identified as being unresponsive to therapeutic antibody treatment. 
     
     
         8 . The method of  claim 1 , wherein the subject has impaired ADCC function. 
     
     
         9 . The method of  claim 1 , wherein (i) said monoclonal antibody is an anti-ErbB2 monoclonal antibody when the subject has breast cancer; (ii) said monoclonal antibody is an anti-CD20 monoclonal antibody when the subject has a B-cell disorder; or (iii) said monoclonal antibody is an anti-EGFR monoclonal antibody when the subject has EGFR-expressing, metastatic colorectal carcinoma, EGFR-expressing head and neck cancer or KRAS mutant cancer. 
     
     
         10 . The method of  claim 9 , wherein the B-cell disorder is lymphoma, leukemia, or rheumatoid arthritis. 
     
     
         11 . The method of  claim 9 , wherein the KRAS mutant cancer is colorectal cancer. 
     
     
         12 . The method of  claim 1 , wherein the therapeutic antibody is rittlximab. 
     
     
         13 . The method of  claim 1 , wherein the therapeutic antibody is trastuzumab. 
     
     
         14 . The method of  claim 1 , wherein the therapeutic antibody is cettlximab. 
     
     
         15 . The method of  claim 1 , wherein the therapeutic antibody is panitumumab. 
     
     
         16 . The method of  claim 1 , wherein the amount sufficient to increase ADCC is between 1 mg/m 2  and 8 mg/m 2 . 
     
     
         17 . The method of  claim 1 , wherein the amount sufficient to increase ADCC is between 2 mg/m 2  and 8 mg/m 2 . 
     
     
         18 . The method of  claim 1 , wherein the amount sufficient to increase ADCC is between 2 mg/m 2  and 6 mg/m 2 . 
     
     
         19 . The method of  claim 1 , wherein the amount sufficient to increase ADCC is between 2 mg/m 2  and 4 mg/m 2 . 
     
     
         20 . The method of  claim 1 , wherein the amount sufficient to increase ADCC is between 0.1 mg/m 2  and 4 mg/m 2 .