Methods of increasing response to cancer radiation therapy

Abstract

Disclosed herein are methods of increasing response to radiation therapy in subjects afflicted with cancer. In some embodiments, the method comprises reducing the ability of an immune suppressor cell (e.g., MDSC) to migrate to the microenvironment of the cancer. In some embodiments, the method further comprises suppressing the migration of the immune suppressor cell to a non-malignant cell and/or suppressing the malignant transformation of the non-malignant cells.

1 . A method of treating a p185her2/neu-associated tumor in a subject comprising administering to the subject a therapeutically effective amount of a first anti-p185her2/neu antibody or an antigen binding portion thereof, a second anti-p185her2/neu antibody or an antigen binding portion thereof, and interferon-gamma (IFNγ). 
     
     
         2 . The method of  claim 1 , wherein the first anti-p185her2/neu antibody or an antigen binding portion thereof and the second anti-p185her2/neu antibody or an antigen binding portion thereof bind to distinct epitopes of the p185 ectodomain. 
     
     
         3 . The method of  claim 1 , wherein the first anti-p185her2/neu antibody is trastuzumab. 
     
     
         4 . The method of  claim 3 , wherein the second anti-p185her2/neu antibody is pertuzumab. 
     
     
         5 . The method of  claim 1 , wherein the first anti-p185her2/neu antibody is pertuzumab. 
     
     
         6 . The method of  claim 1 , comprising administering to the subject a therapeutically effective amount of a radiation or a chemotherapeutic agent. 
     
     
         7 . The method of  claim 6 , wherein the chemotherapeutic agent comprises a taxane. 
     
     
         8 . The method of  claim 7 , wherein the taxane is paclitaxel. 
     
     
         9 . The method of  claim 1 , wherein the p185her2/neu-associated tumor is breast cancer. 
     
     
         10 . A method of prophylactically treating a subject who is predisposed to developing a p185her2/neu-associated tumor comprising administering to the subject a therapeutically effective amount of a first anti-p185her2/neu antibody or an antigen binding portion thereof, a second anti-p185her2/neu antibody or an antigen binding portion thereof, and interferon-gamma (IFNγ). 
     
     
         11 . The method of  claim 10 , wherein the first anti-p185her2/neu antibody or an antigen binding portion thereof and the second anti-p185her2/neu antibody or an antigen binding portion thereof bind to distinct epitopes of the p185 ectodomain. 
     
     
         12 . The method of  claim 10 , wherein the first anti-p185her2/neu antibody is trastuzumab. 
     
     
         13 . The method of  claim 12 , wherein the second anti-p185her2/neu antibody is pertuzumab. 
     
     
         14 . The method of  claim 10 , wherein the first anti-p185her2/neu antibody is pertuzumab. 
     
     
         15 . The method of  claim 10 , comprising administering to the subject a therapeutically effective amount of a radiation or a chemotherapeutic agent. 
     
     
         16 . The method of  claim 15 , wherein the chemotherapeutic agent comprises a taxane. 
     
     
         17 . The method of  claim 16 , wherein the taxane is paclitaxel. 
     
     
         18 . The method of  claim 10 , wherein the p185her2/neu-associated tumor is breast cancer. 
     
     
         19 . The method of  claim 10 , wherein the subject is at risk of relapse or recurrence of the p185her2/neu-associated tumor. 
     
     
         20 . The method of  claim 10 , wherein the method delays the development of the p185her2/neu-associated tumor for a period of at least 30 days.