Scientists use tumor-seeking salmonella to treat brain tumors in rats

DURHAM, N.C., Jan. 11 (UPI) -- Researchers at Duke University are using a strain of salmonella to fight the deadliest form of brain cancer, and finding success in rats.

The team of biomedical engineers at Duke University have developed a way to treat glioblastoma, the most aggressive type of brain cancer, by using Salmonella typhimurium.

The median survival rate of glioblastoma is 15 months, with only 10 percent of patients surviving five years after diagnosis.

Glioblastoma is hard to treat because drugs have difficulty breaking through the blood-brain barrier, a protective sheath separating brain tissue from its blood vessels. Glioblastoma tumors are also challenging to completely remove with surgery, and any remnants left behind spawn new tumors.

The biomedical engineers at Duke genetically-engineered S. typhimurium into a cancer-seeking substance that creates self-destruct orders deep within tumors.

Testing in rat models with severe cases of the disease showed a 20 percent survival rate over 100 days. That is the equivalent of 10 human years, with the tumors going into complete remission.

"Since glioblastoma is so aggressive and difficult to treat, any change in the median survival rate is a big deal," Jonathan Lyon, Ph.D. student at Duke's Pratt School of Engineering, said in a press release. "And since few survive a glioblastoma diagnosis indefinitely, a 20 percent effective cure rate is phenomenal and very encouraging."

The engineers used a detoxified strain of S. typhimurium that was deficient in purine, a vital enzyme, forcing the bacteria to seek supplies from other sources. Tumors are an excellent source of purine so bacteria flock to them.

The team made certain genetic changes so the bacteria would produce two compounds, azurin and p53, that instruct cells to commit suicide.

"A major challenge in treating gliomas is that the tumor is dispersed with no clear edge, making them difficult to completely surgically remove," Ravi Bellamkonda, Vinik Dean of Duke's Pratt School of Engineering and co-author of the study, said in a press release. "And because their natural toxicity has been deactivated, they don't cause an immunological response. At the doses we used in the experiments, they were naturally cleared once they'd killed the tumors, effectively destroying their own food source."

The study was published in Molecular Therapy - Oncolytics.
Amy Wallace

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