A bacterial living therapeutics with engineered protein secretion circuits to eliminate breast cancer cells

Abstract

Cancer therapy often faces limitations due to potential side effects, prompting scientific interest in bacteria-based living cancer treatments. Yet, the complete utilization of bacteria in therapeutic applications confronts engineering hurdles. This thesis focuses on introducing a novel bacterial mechanism specifically intended to target and eliminate breast cancer cells. Our innovative approach involves modifying Escherichia coli (E. coli) to secrete a Shiga toxin called HlyE, a pore-forming protein that binds to HER2 receptors found on breast cancer cells. This binding process is facilitated by a nanobody expressed on the bacterial surface through the Ag43 autotransporter protein system. Our research demonstrates the effective binding of the nanobody to HER2+ cells in laboratory conditions (in vitro). Utilizing the YebF secretion system, we successfully leverage the secretion of HlyE, leading to the eradication of the targeted cancer cells. These outcomes emphasize the significant potential of our engineered bacteria as an innovative and promising strategy for breast cancer treatment. This pioneering approach represents a groundbreaking development in the field of cancer therapeutics. By harnessing the unique properties of bacteria and utilizing advanced engineering techniques, we've succeeded in creating a targeted and potent system capable of attacking breast cancer cells specifically marked by the HER2 receptor. Our study lays a robust foundation for future exploration and development in the realm of bacterial-based cancer therapies, offering potential solutions to the challenges encountered in traditional cancer treatment methods.