Bacteriophage for treatment and prevention of E. coli and B. fragilis infections
Inventors
MORALES, Sandra P. • BILINSKY, Igor P.
Assignees
Publication Number
US-12268720-B2
Publication Date
2025-04-08
Expiration Date
2039-02-07
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Abstract
The present invention relates to a bacteriophage composition comprising one or more (suitably two or more, or three) bacteriophages that target oncogenic (tumorigenic) bacteria, and use of the same for treating or preventing cancer.
Core Innovation
The invention relates to compositions and methods for treating or preventing bacterial-associated cancers through administration of a bacteriophage composition. The composition comprises one or more (preferably at least two) obligately lytic bacteriophages that target and lyse oncogenic or tumorigenic bacteria, particularly Escherichia coli and Bacteroides fragilis associated with various cancers, such as colorectal cancer. The bacteriophages may be specific to certain bacterial strains, including pathogenic or carcinogenic strains, and may be either naturally occurring or non-naturally occurring.
The problem addressed by the invention is the association between bacterial pathogens and carcinogenesis or tumorigenesis in tumors and tissues, and the need for effective methods to treat or prevent cancers that are linked to bacterial infections. Conventional antibacterial agents and cancer therapeutics may have limitations, including the development of bacterial resistance, lack of specificity, and incomplete efficacy against bacteria involved in cancer development.
The core innovation centers on providing bacteriophage compositions that contain one or more obligately lytic bacteriophages, which are capable of precisely targeting and lysing carcinogenic bacteria without broadly affecting the microbiota. The compositions are formulated to minimize the development of bacterial resistance, may exclude bacteriophages capable of generalized transduction or carrying antibiotic resistance genes, and are efficacious in lysing bacterial species associated with cancer, such as pks+ E. coli and enterotoxigenic B. fragilis (ETBF). These compositions can serve as alternatives or adjuncts to conventional antibacterial and cancer therapies.
Claims Coverage
The independent claims encompass three main inventive features, focusing on methods for treating bacterial-associated cancers, methods for treating bacterial infections associated with colorectal cancer, and a bacteriophage composition for human therapeutic use.
Method of treating a bacterial associated cancer or infection with obligately lytic phage composition
A method of treating a bacterial associated cancer or bacterial infection in a patient by administering a composition comprising at least two obligately lytic bacteriophages that infect and lyse either Escherichia coli or Bacteroides fragilis. The bacteriophages are selected from the group consisting of Ec34 (SEQ ID NO:2), Ec35 (SEQ ID NO:3), Ec45 (SEQ ID NO:4), Ec57 (SEQ ID NO:6) for targeting E. coli, and Bf1 (Accession No. 040219-02), Bf2 (Accession No. 040219-03), Bf3 (Accession No. 040219-04), Bf4 (Accession No. 040219-05) for targeting B. fragilis.
Method for treating bacterial infection in colorectal cancer with lytic phage composition
A method for treating a bacterial infection in a patient in need thereof by administering a composition comprising one or more obligately lytic bacteriophages targeting at least one bacterial species associated with colorectal cancer. The composition contains bacteriophages selected from Ec34 (SEQ ID NO:2), Ec35 (SEQ ID NO:3), Ec45 (SEQ ID NO:4), Ec57 (SEQ ID NO:6) (for E. coli), or Bf1, Bf2, Bf3, Bf4 (for B. fragilis).
Human therapeutic bacteriophage composition for treating bacterial infection
A human therapeutic bacteriophage composition formulated for treating a bacterial infection in a subject, comprising one or more obligately lytic bacteriophages with a narrow spectrum of activity against the target bacteria. Each individual bacteriophage is not prone to generalized transduction and does not carry antibiotic resistance genes. The composition is substantially free of bacterial components and comprises a single dosage of 1×10^5 to 1×10^11 PFU of each phage per mL of composition, containing bacteriophages selected from Ec34, Ec35, Ec45, Ec57 (for E. coli) or Bf1, Bf2, Bf3, Bf4 (for B. fragilis).
In summary, the inventive features claim bacteriophage compositions and their use for the treatment or prevention of bacterial-associated cancers or infections, utilizing selected obligately lytic phages specific for Escherichia coli or Bacteroides fragilis, with restrictions on transduction potential and antibiotic resistance, and defined formulation and dosing parameters.
Stated Advantages
The bacteriophage composition can be an alternative to conventional antibacterial agents or cancer therapeutics and overcomes one or more problems associated therewith.
The composition minimizes the development of bacterial resistance through complementation by using multiple distinct bacteriophages.
The bacteriophages can precisely target oncogenic bacteria without broadly destroying other microbiota present in the patient.
The compositions are efficacious in lysing bacteria associated with cancers, including resistant or biofilm-forming strains.
The bacteriophage composition can be utilized as co-treatment or in combination with conventional antibacterial agents or cancer therapeutics.
Documented Applications
Treatment or prevention of bacterial-associated cancers, including colorectal cancer, esophageal cancer, gallbladder cancer, lung cancer, squamous cell carcinoma, bladder cancer, stomach cancer, and MALT lymphoma.
Treatment or prevention of infections by Escherichia coli or Bacteroides fragilis, including pks+E. coli and enterotoxigenic B. fragilis (ETBF) strains.
Modification of the microbial flora in a human by administering bacteriophages with lytic activity against carcinogenic bacteria.
Use as an alternative or adjunct to conventional antibacterial agents or cancer therapeutics, including administration with antibiotics or chemotherapeutics.
Therapeutic use in patients with bacterial infections characterized by biofilms or resistance to antibiotics.
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