JP-2022532162-A5 -

Dates

Publication Date

20230512

Application Date

20200505

Description

Where used herein, all headings are for organizational purposes only and are not intended to limit this disclosure in any way. The contents of individual sections may apply equally to all sections. The embodiments of the present invention include the following: <1> A method for reducing the incidence and/or severity of graft-versus-host disease (GVHD) in subjects requiring reduction, comprising administering an effective amount of a β-lactamase agent. <2> The method according to <1>, wherein the β-lactamase agent has an amino acid sequence that is 95% or more identical to SEQ ID NO: 1 or SEQ ID NO: 6. <3> The method according to <1>, wherein the β-lactamase agent has the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 6. <4> The method according to <1>, wherein the subject is a transplant recipient. <5> The method according to <1>, wherein the subject is a recipient of allogeneic hematopoietic stem cell transplantation. <6> The method according to any one of <1> to <5>, wherein the subject is a recipient of bone marrow cells, peripheral blood cells, or umbilical cord cells. <7> The subject is the method according to any one of <1> to <6>, wherein a β-lactam antibiotic is administered intravenously, or is administered intravenously. <8> The method according to <7>, wherein the β-lactam antibiotic is selected from penicillin (e.g., piperacillin/tazobactam), cephalosporin (e.g., cefepime), and/or carbapenem (e.g., meropenem, imipenem/cilastatin). <9> The GVHD is acute, according to any of the methods described in <1> to <8>. <10> The β-lactamase is administered before transplantation, according to any of the methods described in <4> to <9>. <11> The β-lactamase is administered following transplantation, according to any one of the methods described in <4> to <10>. <12> The method according to any one of <1> to <11>, wherein intestinal dysbiosis is reduced or eliminated in the subject. <13> A method according to any one of <1> to <12> that prevents new colonization (colonization) within the intestinal microbiome of the subject. <14> The method according to any one of <1> to <13>, wherein the expansion of colonization within the intestinal microbiome of the subject is prevented. <15> A method according to any one of <1> to <14> that prevents monodomination of the gut microbiome. <16> The method according to any one of <13> to <15>, wherein the establishment, expansion, or mono-dominance of the microbiome includes one or more types of multidrug-resistant organisms. <17> The aforementioned one or more types of multidrug-resistant organisms include Aeromonas hydrophila, Bacillus (e.g., Bacillus cereus), Bifidobacterium, Bordetella, Borrelia, Brucella, Burkholderia, C. difficile, Campylobacter (e.g., Campylobacter fetus and Campylobacter jejuni), Chlamydia, Chlamydophila, and Clostridium (e.g., Clostridium botulinum) Botulinum), Clostridioides difficile (formerly Clostridium difficile), and Clostridium perfringens), Corynebacterium, Coxiella, Ehrlichia, Enterobacteriaceae (e.g., carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E)), fluoroquinolone-resistant Enterobacteriaceae, Enterococcus (e.g., vancomycin-resistant Enterococcus species, extended-spectrum β-lactam-resistant Enterococcus (ESBL)) , and vancomycin-resistant enterococci (VRE), Escherichia species (e.g., enteroaggregative E. coli, enterohemorrhagic E. coli, enteroinvasive E. coli, enteropathogenic E. coli, enterotoxigenic E. coli (e.g., but not limited to LT and/or ST), E. coli 0157:1-17, and multidrug-resistant E. coli), Francisella species, Haemophilus species, Helicobacter species (e.g., Helicobacter pylori) (e.g., Klebsiella pneumonia and multidrug-resistant Klebsiella), Legionella, Leptospira, Listeria (e.g., Listeria monocytogenes), Morganella, Mycobacterium, Mycoplasma, Neisseria, Orientia, Plesiomonas shigelloides, antibiotic-resistant proteobacteria, Proteus, Pseudomonas, Rickettsia, Salmonella (e.g., Salmonella paratifida) The method according to <16>, selected from Salmonella species and Salmonella typhi, Shigella species (e.g., Shigella species), Staphylococcus species (e.g., Staphylococcus aureus and Staphylococcus species), Streptococcus, Treponema, Vibrio species (e.g., Vibrio cholerae, Vibrio parahaemolyticus, Vibrio species and Vibrio vulnificus), and Yersinia species (e.g., Yersinia enterocolitica). <18> The method according to <17>, which includes the establishment, expansion, or mono-dominance of the microbiome, including the abnormal proliferation of enterococcal species. <19> The establishment, expansion, or mono-dominance of the microbiome is the method according to <18>, including vancomycin-resistant enterococci (VRE). <20> The method according to any one of <1> to <19>, wherein the dose, duration of administration, or frequency of administration of a therapeutic agent for the treatment of GVHD is reduced. <21> The therapeutic agent for treating GVHD is a steroi