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Modified bacterial strain can help treat tumors
Salmonella are usually considered to be dangerous pathogens for diseases. Salmonella enters the body through spoiled food and is able to cause a serious infection there. However, experts have known for a long time that these bacteria also settle specifically in tumors. Scientists have now developed a Salmonella strain that only triggers a harmless infection, but also activates the immune system strong enough to start fighting any tumors that may be present.
The scientists at the Helmholtz Center for Infection Research (HZI) in Braunschweig attempted to use a special property of salmonella for cancer therapy in their investigation. Salmonella infections can usually have life-threatening consequences for humans. However, the experts developed a Salmonella strain that only triggers a harmless infection and can help fight tumors.
Cancer is one of the leading causes of death in people worldwide
Many people die in Germany from the consequences of cancer. Cancer is one of the most common causes of premature death worldwide. Cancer is of increasing importance, especially in a society whose members are getting older and older. However, there is still no effective therapy for many types of cancer tumors.
How does the immune system respond more effectively to tumors?
So far, it has been considered a promising approach to treating cancer to have the human immune system remove the tumors. The experts at the Helmholtz Center for Infection Research (HZI) were therefore looking for ways to make the human immune system more aware of the tumors. This is how a body's defense response is to be achieved. To trigger this effect, the scientists used the bacteria of the Salmonella enterica species.
Salmonella infection can usually be fatal
In people with cancer, the salmonella specifically colonize the tumor tissue. However, there is a major disadvantage: infection with Salmonella can quickly become life-threatening for those affected. "For this type of tumor control, a Salmonella strain must trigger a strong immune response, but it must not be too aggressive to be kept in check," explains Dr. Sebastian Felgner from the Helmholtz Center for Infection Research in a press release on the study results.
Experts are changing the properties of Salmonella
The bacteria were genetically modified step by step by the scientists. The experts tried to achieve an optimal balance between security and an adequate immune response. Various properties of Salmonella have been greatly modified. For example, a component that switches off the musculoskeletal system was affected. This ensures that the mobility of the bacteria is reduced, explains Dr. Felgner continues.
The shell of the bacteria has been modified
In order for the human immune system to be able to recognize the bacteria, certain changes were made in the membrane of the Salmonella by the doctors. For this purpose, certain proteins in the outer shell have been modified, among other things. The experts say that lipopolysaccharides, which consist of sugar and fat chains, are anchored in the membrane. Such molecules are on the surface of the bacteria. They are usually recognized as intruders by the human immune system. In order to enter a host unnoticed, various Salmonella enzymes are able to split off fat chains. In this way, they can hide from the immune system if they are infected. Exactly these enzymes that triggered the release were switched off in the experiment in the Salmonella strain used. As a result of this shutdown, the fat chains on the surface of the bacteria are preserved and the bacteria are still clearly recognizable for the immune system of those affected, explains Dr. Felgner.
Balance between the weakening of the bacteria and the strength of the immune response
The researchers have integrated various genetic changes into their Salmonella strain. Then the experts began to study the therapeutic effects on mice. According to their own information, the scientists have managed to find the right balance between the weakening of the bacteria and the strength of the immune response. Another problem was also solved. If people had previously come into contact with the bacteria, they could have already developed immunity to these bacteria, which would have no effect on the therapeutic Salmonella.
"One problem is that people who have already come into contact with the bacteria have developed immunity to them and may no longer respond to the therapeutic salmonella," says Professor Siegfried Weiß, former head of the HZI Department of Molecular Immunology and now working at the Hannover Medical School (MHH). A so-called therapeutic bacterial strain must be able to overcome the body's protection and salmonella infections are relatively widespread in some regions with poor hygienic conditions. This can make people in the affected countries already immune to salmonella, the expert adds.
Modified Salmonella strain patent pending
Through the various modifications made, the scientists developed a Salmonella strain that also activates the body's defense in mice with immunity to Salmonella. Even tumors that were previously resistant to the Salmonella strain were destroyed by the immune system, says Professor Weiß. A patent has already been filed for the Salmonella strain modified by the doctors. The strain is safe and at the same time effective enough to be used in tumor therapy, explains Dr. Felgner. Now the modified bacterial strain has to be tested in further studies to check its suitability for clinical use, the authors say. (as)