Salmonella – rod like bacteria – are well known highly virulent pathogens. When encountering our immune system they elicit a whole array of reactions some of which feed also back onto the bacteria. Interactions like that between our immune system and Salmonella might pave the way to a completely novel perspective in the fight against cancer.
As soon as our immune system recognizes a foreign substance it reacts fast and powerful. It produces messenger molecules that direct the fine tuning of the immune reaction: they activate or deactivate cells, elicit the production of growth factors and other messenger molecules, start or terminate the immune reaction. Scientists at the HZI investigate such interactions and find very unexpected links.
Our researchers use pathogens against tumors. Many bacteria like Salmonella are able to colonize solid tumors. This colonization results in the death of many tumor cells – a so called necrosis is forming there. This event is supported by substances produced by the immune system in reaction to the bacteria. In such necrotic regions the Salmonella find ideal conditions. They proliferate and destroy the tumor from inside.
Besides these natural reactions of the bacteria, it is also possible to make the bacteria produce therapeutic substances directly in the tumor. They will receive an additional gene that contains the genetic information for the substance. Thus, if the bacteria in the necrotic area are thriving, they will produce the therapeutic compound resulting in a very local chemotherapy. This should enable a very targeted combat against the tumor leaving the healthy tissue untouched. For this goal, it is necessary to find appropriate bacterial control elements so-called promoters that restrict the production of the therapeutic molecules to the cancerous tissue.
The focus of the research at the moment is therefore to define bacterial genes that are active only in the tumor in order to use their promoters. At the same time, the Salmonella need to be attenuated to avoid toxic effects. Not enough, the colonization of the tumor by the bacteria has an additional benefit. It activates the immune system. Due to the lysis of the tumor cells tumor antigens are reaching the draining lymph nodes and the spleen. At the same time the bacteria act as adjuvant and help the immune system.
The combination of these two reactions lead to a tumor-specific immune response. Thus, the immune system recognizes the cancer and attacks it. The residual tumor which is not yet necrotic will now be cleared by immune cells. By this newly defined tumor specific reaction the researchers expect a new possibility to fight against metastases even when they are not yet detectable by modern diagnostic tools. The immune system should now continue to fight against tumor cells that are still hidden in the body and later reoccurring of the same tumor. The individual is practically vaccinated against the defeated tumor.
Dr Siegfried Weiß
Head of Department
+49 531 6181-5100
+49 531 6181-5002
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