Engineered Bacteria Shows Promise in Targeted Cancer Therapy | PLOS Biology

Scientists have engineered a common probiotic bacterium to seek out and destroy tumor cells in mice, delivering a potent cancer drug directly to the site of the disease. The research, published March 17th in the open-access journal PLOS Biology, represents a novel approach to cancer treatment that aims to improve efficacy while reducing systemic side effects.

The team, led by Tianyu Jiang of Shandong University in Qingdao, China, focused on Escherichia coli Nissle 1917 (EcN), a probiotic strain already known for its ability to colonize the gut. Researchers genetically modified EcN to produce Romidepsin (FK228), an FDA-approved drug used to treat certain types of lymphoma. The goal was to create a “living therapy” capable of both targeting tumors and delivering a therapeutic payload.

“By leveraging engineered EcN, we can design a bacteria-assisted, tumor-targeted therapy for the biosynthesis and targeted delivery of small-molecule anticancer agents,” the authors wrote in their publication. The engineered strain achieved an in vitro yield of 1.5 mg/L of Romidepsin, according to the study.

In laboratory tests and in a mouse model of breast cancer, the modified bacteria demonstrated an ability to accumulate within tumors and release the anticancer drug. This targeted delivery system showed improved results compared to the use of the unmodified EcN strain. The researchers observed that the combination of the bacteria’s tumor colonization and Romidepsin’s inherent anticancer properties created a “dual-action cancer therapy.”

The study also indicated a potential reduction in the cardiotoxicity often associated with Romidepsin. By delivering the drug directly to the tumor, the engineered bacteria minimized systemic exposure, potentially lessening harmful side effects. Proteomic analysis revealed that the inflammatory response induced by EcN, combined with the localized production of FK228, contributed to the improved treatment outcomes.

While the results are promising, the researchers caution that significant work remains before this approach can be tested in humans. Further studies are needed to assess potential side effects and to develop strategies for safely controlling and removing the engineered bacteria after treatment.

According to the authors, “Escherichia coli Nissle 1917’s tumor colonization synergizes with Romidepsin’s anticancer activity to form a dual-action cancer therapy.”