Anti-her2 combinations for treating tumors

Abstract

The present invention relates to therapeutic combinations and methods for treating cancers using combination therapy.

1 . A combination, comprising:
 (i) an effective amount of a Her2/Neu binding antagonist antibody; and   (ii) an effective amount of an immunotherapeutic that is capable of activating a human plasmacytoid dendritic cell, myeloid dendritic cell, or NK cell, or a combination thereof, wherein said immunotherapeutic has a structure:   
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The combination of  claim 1 , wherein said Her2/Neu binding antagonist is trastuzumab. 
     
     
         3 . The combination of  claim 1 , wherein said immunotherapeutic is 4-amino-2-(ethoxymethyl)-a,a-di-methyl-1H-imidazo[4,5-c]quinoline-1-ethanol. 
     
     
         4 . The combination of  claim 1 , wherein said combination is capable of providing a systemic effect against cancer or tumor recurrence. 
     
     
         5 . The combination of  claim 1 , further comprising an effective amount of an additional therapeutic agent. 
     
     
         6 . The combination of  claim 5 , wherein said additional therapeutic agent is an anticancer agent. 
     
     
         7 . The combination of  claim 6 , wherein said anticancer agent is an antimetabolite, an inhibitor of topoisomerase I and II, an alkylating agent, a microtubule inhibitor, an antiandrogen agent, a GNRh modulator or mixtures thereof. 
     
     
         8 . The combination of  claim 5 , wherein said additional therapeutic agent is a chemotherapeutic agent selected from the group consisting of tamoxifen, raloxifene, anastrozole, exemestane, letrozole, imatanib, paclitaxel, cyclophosphamide, lovastatin, minosine, gemcitabine, cytarabine, 5-fluorouracil, methotrexate, docetaxel, goserelin, vincristine, vinblastine, nocodazole, teniposide etoposide, gemcitabine, epothilone, vinorelbine, camptothecin, daunorubicin, actinomycin D, mitoxantrone, acridine, doxorubicin, epirubicin, or idarubicin. 
     
     
         9 . The combination of  claim 1 , wherein said immunotherapeutic is of an amount that is capable of:
 (1) inducing IFN-α in an enriched human blood DCs;   (2) inducing TNF-α in an enriched human blood DCs;   (3) inducing IL-12-α in an enriched human blood DCs;   (4) activating CD45 +  immune cells in tumor microenvironment;   (5) activating CD4 +  and CD8 +  T cells in tumor microenvironment;   (6) activating NK cells in tumor microenvironment;   (7) activating plasmacytoid dendritic cells (pDC) and myeloid dendritic cells (mDc) in tumor microenvironment;   (8) activating macrophages and Monocytes in tumor microenvironment; and/or   (9) increasing migratory DCs in draining lymph nodes.   
     
     
         10 . The combination of  claim 1  wherein said effective amount of the immunotherapeutic is from about 0.0005 mg/kg, 0.0006 mg/kg, 0.0007 mg/kg, 0.0008 mg/kg, 0.0009 mg/kg, 0.001 mg/kg, 0.002 mg/kg, 0.003 mg/kg, 0.004 mg/kg, 0.005 mg/kg, 0.006 mg/kg, 0.007 mg/kg, 0.008 mg/kg, 0.009 mg/kg, 0.01 mg/kg, 0.02 mg/kg, 0.025 mg/kg, 0.05 mg/kg, 0.075 mg/kg, 0.1 mg/kg, 0.125 mg/kg, 0.15 mg/kg, 0.175 mg/kg, 0.2 mg/kg, 0.215 mg/kg, 0.25 mg/kg, 0.5 mg/kg, 0.75 mg/kg, 1 mg/kg, 1.25 mg/kg, 1.5 mg/kg, 1.75 mg/kg, 2 mg/kg, or 2.25 mg/kg, to about 2.5 mg/kg, all inclusive, twice daily, once daily, once every two, three, four, five or six days, or once, twice, or three times per week. 
     
     
         11 . The combination of  claim 1  wherein said effective amount of the immunotherapeutic is from about 0.0005 mg/kg, to about 0.0006 mg/kg, 0.0007 mg/kg, 0.0008 mg/kg, 0.0009 mg/kg, 0.001 mg/kg, 0.002 mg/kg, 0.003 mg/kg, 0.004 mg/kg, 0.005 mg/kg, 0.006 mg/kg, 0.007 mg/kg, 0.008 mg/kg, 0.009 mg/kg, 0.01 mg/kg, 0.02 mg/kg, 0.025 mg/kg, 0.05 mg/kg, 0.075 mg/kg, 0.1 mg/kg, 0.125 mg/kg, 0.15 mg/kg, 0.175 mg/kg, 0.2 mg/kg, 0.215 mg/kg, 0.25 mg/kg, 0.5 mg/kg, 0.75 mg/kg, 1 mg/kg, 1.25 mg/kg, 1.5 mg/kg, 1.75 mg/kg, 2 mg/kg, 2.25 mg/kg, or 2.5 mg/kg, all inclusive, twice daily, once daily, once every two, three, four, five or six days, or once, twice, or three times per week. 
     
     
         12 . The combination of  claim 1  wherein said effective amount of the immunotherapeutic is from about 0.0008 mg/kg to about 0.0067 mg/kg, weekly in a human. 
     
     
         13 . The combination of  claim 1 , suitable for administration orally, sublingually, intravenously, intramuscularly, subcutaneously, or intratumorally. 
     
     
         14 . A kit, comprising the combination of  claim 1 .