Probiotics are commensal microbes that can be used to regulate a healthy intestinal microbiota, translating to improved metabolism and immunity. Genetically engineered probiotics have been studied for the treatment of inflammatory bowel disorders such as Crohn’s disease, ulcerative colitis, as well as for diseases linked to hyperactivity of the host immune system. Recently, probiotic cells have been engineered to secrete a luminescent signal upon detection of liver cancer. These luminescent signals are excreted by the kidney and can be measured from patient urine samples. Herein, we present our recent work using engineered probiotics to target colorectal tumor resulting in tumor regression. A combination of two strategies is employed in order to allow effective targeted drug delivery from the engineered probiotic cells to colorectal tumors. Firstly, probiotic cells are engineered to express cancer biomarker-binding proteins on the surface of the probiotic membrane for specific binding to colorectal tumors. Secondly, the probiotic cells are engineered to secrete an enzyme that converts compounds from daily food consumption into anti-cancer compounds. The class of enzyme was screened to have stronger binding affinity to the substrate as well as improved pH and temperature tolerance for better performance in the gastro-intestinal tract. When the enzyme is combined with a secretion tag, the probiotics are able to deliver it to the surface-bound cancer cells. These engineered probiotics have been tested in vitro, causing cell-line specific cancer cell death of up to 95%, as well as in vivo, leading to latent tumor formation and reduced tumor size upon treatment in murine models Our work demonstrates that using binding proteins and enzymatic screening, engineered probiotics can be further enhanced for cancer treatment.

Therapeutic probiotics engineered to target colorectal cancer

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.