The goal of this project is to develop a bacteria-based therapy for cancer. Since conventional radiation and chemotherapies attack cells on the outside of the tumors, another strategy is needed to kill cells in the interior of the tumor. Solid cancerous tumors often have nearly anaerobic cores due to poor blood circulation, and some anaerobic bacteria are known to enter tumor cells and reproduce. If these bacteria can be engineered to produce cytokines that will activate the immune system, then all of the tumor cells could be eliminated. Here we show the successful modification of a bacterial plasmid in Escherichia coli to express and secrete a known human apoptotic factor (TRAIL), which aids in controlled cell death of cancerous cells. Once expression is optimized, this plasmid will be introduced into an attenuated strain of Salmonella enteria Typhimurium, which is known to invade tumor cells. This bacterium can then be tested as a therapy in mouse models of cancer.
This research was supported by the Undergraduate Research Opportunities Program (UROP).
Developing an Anti-Tumor Therapy: Expression of mTRAIL Cytokine in Escherichia coli.
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