Idioma:

Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia

Gurbatri, Candice R ; Radford, Georgette A ; Vrbanac, Laura ; Im, Jongwon ; Thomas, Elaine M ; Coker, Courtney ; Taylor, Samuel R ; Jang, YoungUk ; Sivan, Ayelet ; Rhee, Kyu ; Saleh, Anas A ; Chien, Tiffany ; Zandkarimi, Fereshteh ; Lia, Ioana ; Lannagan, Tamsin R M ; Wang, Tongtong ; Wright, Josephine A ; Kobayashi, Hiroki ; Ng, Jia Q ; Lawrence, Matt ; Sammour, Tarik ; Thomas, Michelle ; Lewis, Mark ; Papanicolas, Lito ; Perry, Joanne ; Fitzsimmons, Tracy ; Kaazan, Patricia ; Lim, Amanda ; Stavropoulos, Alexandra M ; Gouskos, Dion A ; Marker, Julie ; Ostroff, Cheri ; Rogers, Geraint ; Arpaia, Nicholas ; Worthley, Daniel L ; Woods, Susan L ; Danino, Tal

Nature communications, 2024-01, Vol.15 (1), p.646-646, Article 646 [Periódico revisado por pares]

England: Nature Publishing Group

Texto completo disponível

Citações Citado por

Enviar para

Título:
Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia
Autor: Gurbatri, Candice R ; Radford, Georgette A ; Vrbanac, Laura ; Im, Jongwon ; Thomas, Elaine M ; Coker, Courtney ; Taylor, Samuel R ; Jang, YoungUk ; Sivan, Ayelet ; Rhee, Kyu ; Saleh, Anas A ; Chien, Tiffany ; Zandkarimi, Fereshteh ; Lia, Ioana ; Lannagan, Tamsin R M ; Wang, Tongtong ; Wright, Josephine A ; Kobayashi, Hiroki ; Ng, Jia Q ; Lawrence, Matt ; Sammour, Tarik ; Thomas, Michelle ; Lewis, Mark ; Papanicolas, Lito ; Perry, Joanne ; Fitzsimmons, Tracy ; Kaazan, Patricia ; Lim, Amanda ; Stavropoulos, Alexandra M ; Gouskos, Dion A ; Marker, Julie ; Ostroff, Cheri ; Rogers, Geraint ; Arpaia, Nicholas ; Worthley, Daniel L ; Woods, Susan L ; Danino, Tal
Assuntos: Adenoma ; Adenoma - diagnosis ; Adenoma - therapy ; Animal models ; Animals ; Bioengineering ; Clinical trials ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - diagnosis ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - therapy ; CTLA-4 protein ; Double-Blind Method ; E coli ; Engineers ; Escherichia coli - genetics ; Genetic engineering ; Granulocyte-macrophage colony-stimulating factor ; Health services ; Humans ; Mice ; Nanobodies ; Oral administration ; Patients ; PD-L1 protein ; Probiotics ; Prospective Studies ; Salicylates ; Salicylic acid ; Tumors
É parte de: Nature communications, 2024-01, Vol.15 (1), p.646-646, Article 646
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
Descrição: Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC. We next undertake an interventional, double-blind, dual-centre, prospective clinical trial, in which CRC patients take either placebo or EcN for two weeks prior to resection of neoplastic and adjacent normal colorectal tissue (ACTRN12619000210178). We detect enrichment of EcN in tumor samples over normal tissue from probiotic-treated patients (primary outcome of the trial). Next, we develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate. Oral delivery of this strain results in increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. To assess therapeutic potential, we engineer EcN to locally release a cytokine, GM-CSF, and blocking nanobodies against PD-L1 and CTLA-4 at the neoplastic site, and demonstrate that oral delivery of this strain reduces adenoma burden by ~50%. Together, these results support the use of EcN as an orally-deliverable platform to detect disease and treat CRC through the production of screening and therapeutic molecules.
Editor: England: Nature Publishing Group
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia

England: Nature Publishing Group

Buscando em bases de dados remotas. Favor aguardar.