Abstract 6525: Colon cancer screening and treatment with engineered probiotics

Abstract

Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment strategies. Here, we demonstrate selective colonization of CRC tumors with the orally-delivered probiotic E. coli Nissle 1917 (EcN) in genetically-engineered and orthotopic murine models of CRC, and human CRC patients. We subsequently engineer EcN to produce screening and therapeutic molecules, resulting in non-invasive detection of precursor CRC lesions and reduction of tumor burden through local induction of robust anti-tumor immunity. Citation Format: Candice R. Gurbatri, Georgette Radford, Jongwon Im, Courtney Coker, Nicholas Arpaia, Susan L. Woods, Daniel L. Worthley, Tal Danino. Colon cancer screening and treatment with engineered probiotics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6525.

Host evolution improves genetic circuit function in complex growth environments

“…Although E. coli K-12 MG1655 is widely used for development and testing of new synthetic circuits due to its favorable growth rate and easy transformability, it becomes a less suitable host candidate when considering therapeutic applications. Among various bacterial strains explored, E. coli Nissle, a probiotic currently in use for treatment of gastrointestinal disorders, has shown promise in clinical applications due to its favorable safety profile and relevance in areas such as irritable bowel disease (IBD), toxic gut metabolite accumulation, and in particular, treatment and detection of cancers ( 29–32 ). As such, we sought to use ALE to improve circuit behavior in E. coli Nissle in a more complex and physiologically relevant growth environment.…”