2024-02-06 コロンビア大学
◆コロンビア工学部のTal Danino率いる国際研究チームは、遺伝子組み換えされた細菌を用いて口から結腸直腸がん (CRC) を診断・治療する新しいアプローチの基礎を築く論文を『Nature Communications』に発表しました。
◆研究者たちは大腸がんに特有の小さな分子であるサリチレートを産生するように遺伝子組み換えされた大腸菌を開発し、マウスに投与した結果、大腸がんの存在を検出できる可能性が示されました。彼らはさらに、大腸がん患者にエンジニアリングされた大腸菌を投与し、診断的および治療的アプローチの両方を検証する予定です。
<関連情報>
- https://www.engineering.columbia.edu/news/modifying-e-coli-diagnose-and-treat-colorectal-cancer
- https://www.nature.com/articles/s41467-024-44776-4
大腸新生物の検出と治療のための腫瘍コロニー形成大腸菌ニッスル1917の工学的研究 Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia
Candice R. Gurbatri,Georgette A. Radford,Laura Vrbanac,Jongwon Im,Elaine M. Thomas,Courtney Coker,Samuel R. Taylor,YoungUk Jang,Ayelet Sivan,Kyu Rhee,Anas A. Saleh,Tiffany Chien,Fereshteh Zandkarimi,Ioana Lia,Tamsin R. M. Lannagan,Tongtong Wang,Josephine A. Wright,Hiroki Kobayashi,Jia Q. Ng,Matt Lawrence,Tarik Sammour,Michelle Thomas,Mark Lewis,Lito Papanicolas,… Tal Danino
Nature Communications Published:20 January 2024
DOI:https://doi.org/10.1038/s41467-024-44776-4
Abstract
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.
