New study Salmonella as a new therapy for cancer tumors?

Modified bacterial strain may help in the treatment of tumors

Normally Salmonella are considered to be dangerous agents of diseases. The salmonella enter the body via spoiled food and are able to cause a serious infection there. However, it has been known for some time among experts that these bacteria also colonize tumors in a targeted manner. Scientists have now developed a Salmonella strain that causes only a harmless infection, but additionally activates the immune system strong enough to begin fighting any tumors that may be present.

The scientists of the Helmholtz Center for Infection Research (HZI) in Braunschweig tried to use a special property of salmonella for cancer therapy. Normally, Salmonella infections can have life-threatening consequences for humans. However, the experts developed a Salmonella strain that causes only a harmless infection and can help combat tumors.

Cancer is one of the leading causes of death in people worldwide

Many people die in Germany as a result of cancer. Cancer is one of the most common causes of premature death worldwide. Especially in a society whose members are getting older and older, cancers are of increasing importance. However, there is still no effective therapy for many types of cancerous tumors.

How does the immune system respond more effectively to tumors??

So far, it has been considered a promising approach to treat cancer, the human immune system to eliminate the tumors. The experts at the Helmholtz Center for Infection Research (HZI) were therefore looking for ways to make the human immune system more alert to the tumors. Thus, an endogenous defense reaction should be achieved. To trigger this effect, the scientists used the bacteria of the species Salmonella enterica.

Salmonella infection can usually be fatal

In people with cancer, Salmonella colonize specifically the tumor tissue. However, there is a big drawback: Salmonella infection can quickly become life-threatening for those affected. "For this type of tumor control, a Salmonella strain must trigger a strong defense reaction of the immune system, but it must not be too aggressive to be kept in check", explains Dr. med. 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 by the scientists step by step. So the experts tried to achieve an optimal balance between safety and adequate immune response. Various properties of Salmonella have been heavily modified. Affected, for example, was a block that switches off the musculoskeletal system. This ensures that the mobility of the bacteria is reduced, explains Dr. med. Felgner continues.

The envelope of the bacteria has been modified

In order for the human immune system to recognize the bacteria, certain changes have been made in the Salmonella membrane by the medical profession. Among other things, certain proteins in the outer shell were changed. In the membrane lipopolysaccharides are anchored, which consist of sugar and fat chains, say the experts. Such molecules are located on the surface of the bacteria. They are usually recognized by the human immune system as intruders. In order to invade a host unnoticed, various Salmonella enzymes are able to cleave off fat chains. This way, they can hide from the immune system during an infection. Exactly these cleavage-eliciting enzymes were eliminated in the experiment on the Salmonella strain used. Through this shutdown, the fat chains on the surface of the bacteria were preserved and the bacteria continue to be easily recognizable for the immune system of those affected, explains Dr. med. Felgner.

Balance between attenuation of the bacteria and the strength of the immune reaction

The researchers have integrated several genetic changes into their Salmonella strain. Then the experts began to investigate the therapeutic effect on mice. The scientists say it has managed to find the right balance between the attenuation of the bacteria and the strength of the immune response. In addition, another problem could be solved. If people had previously come into contact with the bacteria, they could have already developed an immunity against 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, formerly 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 own protection and salmonella infections are relatively widespread in some regions with poor hygienic conditions. This can cause 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 activates the body's own defense even in mice with Salmonella immunity. Even tumors that were previously resistant to the salmonella strain were destroyed by the immune system, says Professor Weiß. The Salmonella strain modified by the physicians has already been patented in the meantime. The strain is safe and at the same time effective enough to be used in tumor therapy. Felgner. Now the modified bacterial strain will have to be tested in further studies to verify its suitability for clinical use, say the authors. (As)