“Our bacterial carrier has a mutation in the msbB
gene that…impedes systemic toxicity,” Dr. Bellamkonda, adding that not only has the strain been used successfully in mouse studies, but that it has also been used in clinical trials with human patients with another form of cancer. Unfortunately, those trials did indicate that the bacterial strain alone without its load of cancer-fighting compounds cannot cause tumor cells to start killing themselves; that clinical trial is what led to this study, in which the S. typhimurium
was bioengineered to express a protein that creates an “apoptotic” effect in tumors, meaning that it causes tumor cells, specifically, to, essentially, commit suicide. While instigating apoptosis is not a new method of attacking GBM tumors, past suboptimal methods of delivery have previously minimized the effectiveness of the strategy. “Absence of an efficient delivery system into solid tumors has dwarfed the effectiveness of these therapies,” Dr. Bellamkonda said. In this specific study, in addition to having a tumor-specific, apoptotic gene, the Salmonella
bacterium was also designed to express a protein called Azurin, which has proven effective in inciting cancer-cell suicide, but is not able to penetrate GBM cells on its own.
When Dr. Bellamkonda and his team injected test animals with the engineered bacterium, test subjects had a survival rate of 19% compared with no survival of untreated test subjects. Although the span of time between the median survival span of the control group (26 human days) and the test group (29 days) may seem fairly short, half of the rats who received the treatment showed evidence of tumor suppression. Furthermore, according to research
published in the International Journal of Preventative Medicine
, one “rat day” translates to roughly 35 human days, meaning that a mere additional three 24-hour spans in a rat life could be equivalent to more than three months in human life extension, if not more. This indicates a clear potential for extending lifespan and allowing for other treatment options to have time to work as well. The researchers also noted that treated rats did not show any signs of illness: essentially, they did not have food poisoning as a result of the salmonella treatment.
The scientists concluded that the S. typhimurium
strain designed to deliver the combination therapy from the modified gene and Azurin is an “advantageous” model when treating GBM because “drug diffusion is a major impediment to successful treatment” of this condition. Because S. typhimurium
are motile, they can specifically target GBM on location and optimize drug delivery. The researchers’ next step will be to program the bacterium to produce even stronger drugs that will produce more significant reactions in the targeted tumors.
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