Bacterial Living Therapeutics with Engineered Protein Secretion Circuits to Eliminate Breast Cancer Cells

Cancer therapy can be limited by potential side effects, and bacteria-based living cancer therapeutics have gained scientific interest in recent years. However, the full potential of bacteria as therapeutics has yet to be explored due to engineering challenges. In this study, we present a bacterial device designed to specifically target and eliminate breast cancer cells. We have engineered <i>Escherichia coli</i> (<i>E. coli</i>) to bind to HER2 receptors on breast cancer cells while also secreting a toxin, HlyE, which is a pore-forming protein. The binding of <i>E. coli</i> to HER2 is facilitated by a nanobody expressed on the bacteria's surface <i>via</i> the Ag43 autotransporter protein system. Our findings demonstrate that the nanobody efficiently binds to HER2+ cells <i>in vitro</i>, and we have utilized the YebF secretion tag to secrete HlyE and kill the target cancer cells. Overall, our results highlight the potential of our engineered bacteria as an innovative strategy for breast cancer treatment.