Cancer Killing Probiotics with High Specificity: Adhere, Quorum Sense, and Kill, Remy Garcia-Kakebeen, UG '27, Ryan Miner, UG '27, Jingjing Wang, UG '26 (4A06F438)
The motivation of our project is to create a treatment that would isolate and attack cancer cells rather than both cancerous and non-cancerous cells. The impact of this would be profound, as patients would experience fewer side effects due to less damage to their healthy cells. We plan on differentiating colon cancer cells from normal cancer cells by their overexpression of Epidermal Growth Factor Receptors (EGFR), a characteristic found in 60%-80% of colon cancer cases. EGFR is a transmembrane protein that promotes growth when interacting with Epidermal Growth Factor (EGF). We plan to engineer a probiotic that can target the overexpression of EGFR, with the steps of binding cancer, confirmation with other bacteria that the cell they are bound to is a cancer cell, and then secretion of a cancer-killing immunotoxin. To bind, we will engineer the bacteria to have protruding EGFR nanobodies that can bind to EGFR without activating it. This will allow our engineered probiotic to bind to cancer cells at a higher concentration since there are more binding locations on cancer cells than on normal cells. Then we will utilize quorum sensing, a concentration-based way of bacterial communication. Once the concentration of bacteria is high enough to produce the signal necessary, the bacteria will respond by producing and secreting our immunotoxins to kill the cancer cells. This will only occur on cancer cells because our bacteria will only bind to cancer cells above the concentration threshold while binding below the concentration threshold on normal cells.