Treatment of cancer by manipulation of commensal microflora

Abstract

Provided herein are methods of treatment and/or prevention of cancer by manipulation of commensal microflora. In particular, the amount, identity, presence, and/or ratio of microflora (e.g., gut microflora) in a subject is manipulated to facilitate one or more co-treatments.

1 . A method of treating cancer in a human subject comprising co-administering to the subject an immune checkpoint inhibitor wherein the immune checkpoint inhibitor is an antibody, and a bacterial formulation comprising bacteria of the genus  Bifidobacterium , wherein the bacterial formulation comprises bacteria selected from the group consisting of  Bifidobacterium animalis  and  Bifidobacterium  breve. 
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein at least 90% of the bacteria in the bacterial formulation are of the genus  Bifidobacterium.    
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein the bacterial formulation is administered by oral administration. 
     
     
         7 . The method of  claim 1 , wherein the bacterial formulation comprises at least 5×10 6  CFU of bacteria of the genus  Bifidobacterium.    
     
     
         8 .- 18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein the immune checkpoint inhibitor is administered by intravenous injection, intramuscular injection, intratumoral injection or subcutaneous injection. 
     
     
         20 .- 29 . (canceled) 
     
     
         30 . The method of  claim 1 , wherein the immune checkpoint inhibitor is selected from the group consisting of pembrolizumab, pidilizumab, AMP-224, AMP-514, TSR-042, RG-7446, BMS-936559, BMS-936558, STI-1110, MK3475, CT-011, MPDL3280A, MEDI-4736, MSB-0020718C, AUR-012 and STI-A1010. 
     
     
         31 . The method of  claim 1 , wherein the immune checkpoint inhibitor is an anti-PD-L1 antibody. 
     
     
         32 . The method of  claim 31 , wherein the immune checkpoint inhibitor is selected from the group consisting of BMS-936559, RG-7446, MEDI-4736, MSB-0010718C and STI-A1010. 
     
     
         33 . The method of  claim 1 , wherein the immune checkpoint inhibitor is an anti-PD-1 antibody. 
     
     
         34 . The method of  claim 33 , wherein the anti-PD-1 antibody is selected from the group consisting of BMS-936558, pembrolizumab, pidilizumab, AMP-224, TSR-042, STI-1110 and MPDL3280A. 
     
     
         35 . The method of  claim 1 , wherein the immune checkpoint inhibitor is an anti-CTLA-4 antibody. 
     
     
         36 . The method of  claim 1 , wherein the immune checkpoint inhibitor is pembrolizumab and the bacterial formulation comprises  B. breve.    
     
     
         37 . The method of  claim 1 , wherein the immune checkpoint inhibitor is MSB-0010718C and the bacterial formulation comprises  B. breve.    
     
     
         38 . The method of  claim 1 , wherein the immune checkpoint inhibitor is MSB-0010718C and the bacterial formulation comprises  B. bifidum.    
     
     
         39 . The method of  claim 1 , wherein the cancer is a solid tumor cancer. 
     
     
         40 . The method of  claim 39 , wherein the solid tumor cancer is a melanoma. 
     
     
         41 . The method of  claim 1 , wherein the immune checkpoint inhibitor is an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, and a bacterial formulation comprising bacteria of the genus  Bifidobacterium , wherein at least 90% of the bacteria in the bacterial formulation are of a single species selected from the group consisting of  Bifidobacterium  animalis,  Bifidobacterium bifidum , and  Bifidobacterium breve , and wherein the treatment increases CD8+ tumor-antigen specific T cells within the cancer.