Methods and compositions for detecting risk of cancer relapse

Abstract

The present invention relates to methods and compositions for reducing the risk of cancer relapse in a subject who has received cancer treatment. It is based, at least in part, on the discovery that a restricted fraction of the gut microbiota, including the bacteria Streptococcus anginosus, Parvimonas micra, Acidaminococcus intestini, Eubacterium limosum, Clostridium glycyrrhizinilyticum, Desulfosporosinus lacus, Eubacterium biforme, Anaerofustis stercorihominis, Pseudoramibacter alactolyticus, Peptococcus niger, Armatimonas rosea, Saccharofermentans acetigenes, Finegoldia magna, Levyella massiliensis, Gallicola barnesae, Murdochiella asaccharolytica , and Eubacterium brachy are associated with a reduced risk of cancer relapse.

1 . A pharmaceutical composition comprising one or more isolated bacteria or spores thereof, wherein the isolated bacteria or spores thereof comprise a 16S rRNA sequence that has between about 85 and 100% identity with a nucleic acid sequence described by any one of SEQ ID NOS: 1-17, and further comprising a biocompatible pharmaceutical carrier. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the isolated bacteria or spores thereof comprise a 16S rRNA sequence described by one or more of SEQ ID NOS: 1-17, or comprise a 16S rRNA sequence having about 97% identity with one or more of SEQ ID NO: 1-17. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the isolated bacteria or spores thereof is selected from the group consisting of  Streptococcus anginosus, Parvimonas micra, Acidaminococcus intestini, Eubacterium  limosum,  Clostridium glycyrrhizinilyticum, Desulfosporosinus lacus, Eubacterium biforme, Anaerofustis stercorihominis, Pseudoramibacter alactolyticus, Peptococcus niger, Armatimonas rosea, Saccharofermentans acetigenes, Finegoldia magna , Levyella  massiliensis, Gallicola barnesae, Murdochiella asaccharolytica, Eubacterium brachy , and a cluster comprising any one or more of the foregoing bacteria. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the composition is formulated for oral, nasogastric, or rectal administration,
 wherein the composition optionally comprises a probiotic bacteria, probiotic yeast, or a combination thereof; a prebiotic; a postbiotic; an antibiotic; or combination thereof, and   wherein the composition is optionally a liquid, suspension, dried powder, tablet, capsule or food product.   
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the one or more isolated bacteria or spores thereof are recombinant bacteria, or progeny thereof, wherein the recombinant bacteria or spores optionally comprise one or more exogenous nucleic acids encoding a protein that confers antibiotic sensitivity or resistance to the recombinant bacteria or spores. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the one or more isolated bacteria or spores thereof are present in an amount that can reduce the risk of cancer relapse in a subject administered the composition. 
     
     
         7 . A method for reducing the risk of cancer relapse and/or increasing likelihood of survival from a cancer relapse in a subject, comprising administering, to a subject in need of such treatment, an effective amount of a pharmaceutical composition comprising one or more isolated bacteria or spores thereof, wherein the isolated bacteria or spores thereof comprise a 16S rRNA sequence that has between about 85 and 100% identity with a nucleic acid sequence described by any one of SEQ ID NOS: 2-17, and further comprising a biocompatible pharmaceutical carrier. 
     
     
         8 . The method of  claim 7 , wherein the subject has had a hematopoietic stem cell transplantation (HSCT), wherein the HSCT is optionally an allogenic hematopoietic stem cell transplantation (allo-HSCT), and wherein the allo-HSCT is optionally a T-cell replete allo-HSCT. 
     
     
         9 . The method of  claim 7 , wherein the composition is administered in an amount effective to decrease the presence of  Enterococcus faecium  in the subject, and/or decrease the amount of  Enterococcus faecium  toxin in the subject. 
     
     
         10 . The method of  claim 7 , further comprising identifying a subject at risk of cancer relapse comprising
 obtaining an intestinal microbiota sample from a subject and determining the level of one or more bacteria or spores thereof comprising a 16S rRNA sequence that has between about 85 and 100% identity with a nucleic acid sequence of any one of SEQ ID NOS: 1-17 present in the intestinal microbiota sample;   comparing the level of the one or more bacteria or spores thereof in the sample with a reference bacteria level; and   administering the composition to the subject when the level of the one or more bacteria or spores thereof in the sample is lower than the bacteria reference level.   
     
     
         11 . The method of  claim 7 , further comprising identifying a subject at risk of cancer relapse comprising
 obtaining an intestinal microbiota sample from a subject and determining the level of  Enterococcus faecium  bacteria present in the intestinal microbiota sample;   comparing the level of the bacteria in the sample with a reference bacteria level; and   administering the composition to the subject when the level of bacteria in the sample is greater than the bacteria reference level.   
     
     
         12 . (canceled) 
     
     
         13 . A method of diagnosing a subject having a risk of cancer relapse comprising
 obtaining an intestinal microbiota sample from a subject and determining the level of one or more of  Enterococcus faecium, Streptococcus anginosus, Parvimonas micra, Acidaminococcus intestini, Eubacterium  limosum,  Clostridium glycyrrhizinilyticum, Desulfosporosinus lacus, Eubacterium biforme, Anaerofustis stercorihominis, Pseudoramibacter alactolyticus, Peptococcus niger, Armatimonas rosea, Saccharofermentans acetigenes, Finegoldia magna, Levyella massiliensis, Gallicola barnesae, Murdochiella asaccharolytica , or  Eubacterium brachy  bacteria or one or more bacteria comprising a 16S rRNA sequence that has between about 85 and 100% identity with a nucleic acid sequence described by any one of SEQ ID NOS: 1-17, present in the intestinal microbiota sample;   comparing the level of the bacteria in the sample with a reference bacteria level; and   diagnosing the subject as having a risk of cancer relapse (i) when the level of the  Enterococcus faecium  bacteria in the sample is greater than the bacteria reference level and/or (ii) when the level of one or more of  Streptococcus anginosus, Parvimonas micra, Acidaminococcus intestini, Eubacterium  limosum,  Clostridium glycyrrhizinilyticum, Desulfosporosinus lacus, Eubacterium biforme, Anaerofustis stercorihominis, Pseudoramibacter alactolyticus, Peptococcus niger, Armatimonas rosea, Saccharofermentans acetigenes, Finegoldia magna, Levyella massiliensis, Gallicola barnesae, Murdochiella asaccharolytica , or  Eubacterium brachy  bacteria or one or more bacteria comprising a 16S rRNA sequence that has between about 85 and 100% identity with a nucleic acid sequence described by any one of SEQ ID NOS: 1-17 in the sample is lower than the bacteria reference level.   
     
     
         14 . The method of  claim 13 , wherein the subject has had a hematopoietic stem cell transplantation (HSCT). 
     
     
         15 . The method of  claim 13 , further comprising administering cancer therapy to the subject diagnosed as having a risk of cancer relapse,
 wherein the cancer therapy optionally comprises surgery; radiation therapy; chemotherapy; immunotherapy; stem cell therapy; cellular therapy; probiotic bacteria, probiotic yeast, or a combination thereof prebiotic; postbiotic; antibiotic; or a combination thereof.   
     
     
         16 . The method of  claim 15 , wherein the probiotic bacteria comprises one or more isolated bacteria or spores thereof comprising a 16S rRNA sequence that has between about 85 and 100% identity with a nucleic acid sequence described by any one of SEQ ID NOS:1-17, and further comprising a biocompatible pharmaceutical carrier. 
     
     
         17 . A kit comprising the composition of  claim 1  and/or comprising one or more agents for detecting the abundance of one or more bacteria or spores thereof comprising a 16S rRNA sequence that has between about 85 and 100% identity with a nucleic acid sequence described by any one of SEQ ID NOS:1-17 in an intestinal microbiota sample. 
     
     
         18 .- 26 . (canceled)