Salmonella can help in the fight against glioblastoma
Anna Stavina, XX2 century, based on the materials of Duke University: Tumor-Seeking Salmonella Treats Brain Tumors
Scientists have genetically modified salmonella, a bacterium that causes food poisoning. Now these microorganisms will be engaged in the search and destruction of tumors, which, as the authors hope, can help to cope with the most dangerous form of brain cancer.
Doctors are in urgent need of new approaches to the treatment of patients with glioblastoma, the most aggressive type of brain tumors.
The blood-brain barrier separating the brain and blood vessels makes it difficult to fight glioblastoma with medications. And with the help of surgery, it is not easy to cope with this form of cancer, because even tiny fragments of glioblastoma remaining in the body inevitably lead to the appearance of new tumors.
Even with the use of the most modern methods of treatment, the average life expectancy of patients after receiving a diagnosis is only about 15 months. Less than 10% of patients cross the 5-year milestone.
Scientists from Duke University decided to create a new approach to glioblastoma therapy. To do this, they genetically modified the bacterium Salmonella typhimurium, adapting it to search for and destroy tumors.
Experiments on rats with advanced forms of the disease showed that the average 100-day survival rate of animals after such treatment was 20%. In terms of human life expectancy, 100 days is equivalent to approximately 10 years.
In earlier studies, it was discovered quite by chance that in the presence of bacteria in the body, the immune system can learn to recognize tumor cells and attack them. However, subsequent clinical trials using neutralized strains of S.typhimurium have shown that the bacteria themselves are ineffective.
To turn ordinary salmonella into a means to fight the tumor, a group of researchers selected a neutralized strain of S. typhimurium, also distinguished by a deficiency of the vital compound purine. The absence of purine forced bacteria to look for it in the external environment. Tumors turned out to be an excellent source of this compound, which made them an attractive target for modified S.typhimurium.
Then the scientists genetically modified the bacteria once again, now to make them produce the proteins azurin and p53. These substances cause cells to commit "suicide", but only when there is a shortage of oxygen.
Since tumor cells are actively dividing, there is usually little oxygen in their environment.
"Surgical treatment of gliomas is difficult because such tumors do not have clear edges, and it is difficult to remove them completely," says one of the authors of the study, Ravi Bellamkonda. – Therefore, the creation of bacteria capable of independently searching for neoplasms, moving to them and releasing antitumor proteins exclusively in an environment rich in purine, but poor in oxygen, looks promising. In the "doses" that we used during the experiments, the bacteria naturally disappeared from the body after the tumor died. In fact, the microorganisms were destroying their own food source."
The results of the work were published in the publication Molecular Therapy – Oncolytics (Mehta et al., Bacterial Carriers for Glioblastoma Therapy).
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