Tumor antigen specific antibodies and tlr3 stimulation to enhance the performance of checkpoint interference therapy of cancer

Abstract

The present disclosure relates to a method for inhibiting cancer tumor growth in a patient by administering to the patient a therapeutic monoclonal antibody specific for a tumor associated antigen in combination with at least one immunostimulatory compound, and at least one immune homeostatic checkpoint inhibitor. Also disclosed are uses, compositions and kits thereof.

1 - 107 . (canceled) 
     
     
         108 . A method for inhibiting growth of a cancer expressing MUC1 on cancer cell surface in a patient comprising administering to the patient a therapeutic monoclonal antibody specific to MUC1, a TLR3 agonist, and an immune homeostatic checkpoint inhibitor, wherein:
 the therapeutic monoclonal antibody specific to MUC1 is (1) monoclonal antibody AR20.5; or (2) a monoclonal IgE antibody having a heavy chain variable region encoded by SEQ ID NO: 1 and a light chain variable region encoded by SEQ ID NO:2; and the TLR3 agonist is polyICLC.   
     
     
         109 . The method of  claim 108 , wherein the therapeutic monoclonal antibody specific to MUC1 is monoclonal antibody 3C6.hIgE. 
     
     
         110 . The method of  claim 108 , wherein the therapeutic monoclonal antibody specific to MUC1 is monoclonal antibody AR20.5 or monoclonal antibody 3C6.hIgE, or a combination thereof. 
     
     
         111 . The method of  claim 108 , wherein the therapeutic monoclonal antibody specific to MUC1 is a murine monoclonal antibody or a chimeric monoclonal antibody. 
     
     
         112 . The method of  claim 111 , wherein the therapeutic monoclonal antibody specific to MUC1 has a constant region that is of human origin. 
     
     
         113 . The method of  claim 108 , wherein the cancer is pancreatic cancer, breast cancer, colorectal cancer, ovarian cancer, renal cancer, prostate cancer, bladder cancer, gastrointestinal cancer, lung cancer, or multiple myeloma. 
     
     
         114 . The method of  claim 108 , comprising:
 (a) administering a therapeutically effective amount of the therapeutic monoclonal antibody specific to MUC1;   (b) administering a therapeutically effective amount of the TLR3 agonist after step (a); and   (c) administering a therapeutically effective amount of the anti-PD-L1 antibody, after step (b).   
     
     
         115 . The method of  claim 114 , wherein step (b) is performed 1 or more days after step (a). 
     
     
         116 . The method of  claim 114 , wherein step (c) is performed 1 or more days after step (b). 
     
     
         117 . The method of  claim 108 , wherein the immune homeostatic checkpoint inhibitor is an anti-PD-L1 antibody. 
     
     
         118 . The method of  claim 117 , wherein the anti-PD-L1 antibody comprises any one of monoclonal antibody 10F.9G2, BMS-936559 antibody, MPDL3280A (atezolizumab) antibody, MEDI-4736 antibody, MSB0010718C antibody or combinations thereof.