Anti-cancer oncolytic virus combination therapies and elite responder selection platforms

Abstract

Therapeutic methods for administering gut microbiota and oncolytic viruses to a subject are provided. The gut microbiota serve to pre-condition, the subject's immune system to antitumor responses and augments anticancer activity of the oncolytic vims. Combinations of the gut, microbiota and viruses and uses thereof for treating and preventing cancer are provided. The present disclosure also provides methods for building elite responder selection platforms through hierarchical clustering analysis of genomic profiles for human gut microbiome.

1 - 21 . (canceled) 
     
     
         22 . A method of treating cancer comprising:
 orally administering to a subject an effective amount of about 10 9  to 10 11  cfu of gut microbiota of the genus  Bifidobacterium ; and   from about one week to two months after the gut microbiota are administered, intravenously or intratumorally administering to the subject an effective amount of about 10 5  to 10 10  pfu of an oncolytic ORF virus having anticancer activity and that selectively targets tumor cells;   wherein the gut microbiota pre-conditions the subject's immune system to antitumor responses and augments the anticancer activity of the oncolytic ORF virus.   
     
     
         23 . The method according to  claim 22 , wherein the cancer is a type of cancer having a high degree of de novo mutations. 
     
     
         24 . The method according to  claim 22 , wherein the cancer is melanoma, lung cancer, kidney cancer, glioma, triple negative breast cancer, or renal cancer. 
     
     
         25 . The method according to  claim 22 , wherein the oncolytic ORF virus is administered about one month after the gut microbiota is administered. 
     
     
         26 . The method according to  claim 22 , wherein the subject is a mammal. 
     
     
         27 . The method according to  claim 22 , wherein the subject is a human. 
     
     
         28 . A method for augmenting the anticancer activity of an oncolytic ORF virus, comprising:
 orally administering to a subject an effective amount of about 10 9  to 10 11  cfu of gut microbiota of the genus  Bifidobacterium  to pre-condition the subject's immune system to antitumor responses; and   administering to the subject an effective amount of oncolytic ORF virus that selectively targets tumor cells;   wherein the pre-condition created by the gut microbiota augments the anticancer activity of the oncolytic ORF virus.   
     
     
         29 . A kit for the treatment and prevention of cancer, comprising:
 a pharmaceutical composition comprising gut microbiota that pre-condition a subject's immune system to antitumor responses;   a pharmaceutical composition comprising an oncolytic virus having anticancer activity and that selectively targets tumor cells; and   instructions for sequentially administering the gut microbiota and oncolytic virus;   wherein the gut microbiota augments the anticancer activity of the oncolytic virus.   
     
     
         30 . A kit according to  claim 29 , wherein the cancer is a type of cancer having a high degree of de novo mutations. 
     
     
         31 . A kit according to  claim 29 , wherein the cancer is melanoma, lung cancer, kidney cancer, glioma, triple negative breast cancer, or renal cancer. 
     
     
         32 . A kit according to  claim 29 , wherein the gut microbiota comprises  Bifidobacterium.    
     
     
         33 . A method of treating cancer comprising:
 (A) orally administering to a human subject an effective amount of commensal gut microbiota of the genus  Bifidobacterium  in an effective amount of about 10 9  to 10 11  cfu; and   (B) 1 week to 2 months after step (A), administering to the subject oncolytic POV-601 virus, which has anticancer activity and which selectively targets tumor cells, in an effective amount of about 10 5  to 10 10  pfu;   wherein the gut microbiota pre-conditions the subject's immune system to antitumor responses and augments the anticancer activity of the oncolytic virus.   
     
     
         34 . The method according to  claim 33 , wherein the cancer is melanoma. 
     
     
         35 . The method according to  claim 33 , wherein the cancer is lung cancer. 
     
     
         36 . A method of treating cancer comprising:
 (A) orally administering to a human subject an effective amount of commensal gut microbiota of the genus  Bifidobacterium  in an effective amount of about 10 9  to 10 11  cfu; and   (B) 1 week to 2 months after step (A), administering to the subject oncolytic POV-801 virus, which has anticancer activity and which selectively targets tumor cells, in an effective amount of about 10 5  to 10 10  pfu;   wherein the gut microbiota pre-conditions the subject's immune system to antitumor responses and augments the anticancer activity of the oncolytic virus.   
     
     
         37 . The method according to  claim 36 , wherein the cancer is melanoma. 
     
     
         38 . The method according to  claim 36 , wherein the cancer is lung cancer. 
     
     
         39 . The method of  claim 22 , wherein the  Bifidobacterium  is PGM-001.