Researchers from Duke University have genetically engineered a strain of salmonella, which usually causes food poisoning, to fight against the most aggressive and deadliest form of brain cancer, glioblastoma.
Their research, published in the journal Molecular Therapy-Oncolytics, showed genetically modifying the bacterium Salmonella typhimurium could turn it into cancer-seeking missile that is capable of producing self-destruct orders deep within the tumors.
"A major challenge in treating gliomas is that the tumor is dispersed with no clear edge, making them difficult to completely surgically remove," said Ravi Bellamkonda, Vinik Dean of Duke's Pratt School of Engineering and corresponding author of the paper, in a press release. "So designing bacteria to actively move and seek out these distributed tumors, and express their anti-tumor proteins only in hypoxic, purine rich tumor regions is exciting."
For the study, the researchers genetically engineered Salmonella typhimurium to deactivate its natural toxicity. The researchers also modified the bacteria so that it could produce two compounds called Azurin and p53 that instruct cells to commit suicide. However, the two compounds can only be produced in low oxygen environment. And due to the energetic multiplication of cancerous cells, the area within and around the tumors are unusually low.
The modified bacteria were then injected directly into the brain of rat models. All the rats showed initial signs of improvement after the treatment. However, 80 percent of them did not survive. On the other hand, the remaining 20 percent have complete tumor regression and have their life extended 100 days, which translates to roughly 10 human years.
The researchers are still not sure what causes the ineffectiveness of the modified bacteria in some of the rat models The researchers argued that the ineffectiveness of the bacteria was likely due to inconsistencies in the penetration of the bacteria. Another possible explanation for the ineffectiveness could be that the tumor growth is outpacing the bacteria.
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