B. hercules
------The Terminator of Colon Cancer

Millions of cancer patients around the world currently depend on conventional cancer therapies to extend their lives. These conventional therapies, composed of surgery, radiotherapy and chemotherapies, all have their own limitations and shortcomings. Short-term and long-term side effects include vomiting, hair loss, organ failure, or even induction of a second tumor brought about by the spreading toxicity of anti-tumor chemicals in the circulatory system, thus prompting active research into alternative cancer therapies. We, the 2012 HKUST iGEM team, have chosen to focus on colorectal carcinomas, the fourth most common cancer type around the world, as our study object. We aim to use genetically modified Bacillus subtilis to execute targeted drug delivery to cancer cells in the intestinal tract, offering an advantage of minimal harm of the drug to normal colon epithelial cells.

Our project hopes to engineer B. subtilis to enable them to recognize colon carcinomas. This specific targeting is to be achieved by expressing a colon tumor specific binding peptide on the cell wall using a cell wall binding system.

After binding, an anti-tumor chemokine is to be synthesized and secreted from the bacterial cells with the help of a signaling peptide fused to the protein. To minimize over-production of this tumor suppressor, an inducible production system is introduced. This option of external inducible control will allow us to initiate chemokine release at a time when optimum effect can be achieved; that is, when the killer bacteria are close enough to the colon cancer cells.

Finally, in consideration of both biosafety issues and the possible harm from an over-dosage of antitumor drug, a toxin-antitoxin system is to be employed in our bacterial vector. This system is supposed to provide a minimum threshold of antitumor drug production and at the same time, minimizing the risk of plasmid lateral transfer among gut flora.

Why B. hercules?