New bacteriophage-related therapeutic strategies for colitis and colorectal cancer

Patient sample and mouse studies suggest an E. coli bacteriophage cocktail could help treat bacteria-aggravated colorectal cancer and blockade of host-bacteriophage interactions via inhibition of IFNγ or TLR9 could help treat colitis. In ulcerative colitis (UC) patients, gut counts of Caudovirales bacteriophages were higher than in healthy volunteers and bacteriophage counts were associated with high gut levels of IFNγ and poor response to fecal microbiome transplant (FMT). In a mouse model of E. coli bacteriophage-driven colitis, knockout of IFNγ or TLR9, through which bacteriophages induce IFNγ production, decreased disease severity compared with normal expression of IFNγ and TLR9. In a mouse model of E. coli-aggravated colorectal cancer, an oral E. coli bacteriophage cocktail decreased tumor size and increased survival compared with vehicle. Next steps could include testing anti-TLR9 or anti-IFNγ antibodies in the colitis model and testing other bacteriophages in colorectal cancer models.

Novimmune S.A. and Swedish Orphan Biovitrum AB have Gamifant emapalumab-lzsg (NI-0501), a human mAb against IFNγ, approved for primary hemophagocytic lymphohistiocytosis (HLH)...