EU-funded researchers hunt down tumour killers using bacteria
Infamous bacteria impacting our lives are Salmonellae, usually found in chicken and eggs. But are they getting too much of a bad rap? EU-funded researchers in Germany may have actually succeeded in putting a positive spin on Salmonellae following the discovery that the bacteria can migrate into solid tumours and destroy them. The findings are published in the journal Public Library of Science (PLoS) ONE. The research is funded in part by the CLINIGENE and MIDITRAIN projects. CLINIGENE received funding totalling EUR 12 million, and MIDITRAIN was supported with more than EUR 2 million in financing.
According to Drs Sara Bartels and Siegfried Weiss of the Helmholtz Centre for Infection Research (HZI) in Brunswick, Germany, the bacteria can enter and destroy malignant tissue thanks to a messenger substance called 'tumour necrosis factor alpha' (TNF-alpha). Because the blood vessels in the diseased area have become permeable, blood can flow from the vessels into the malignant tissue, thus effectively killing the tumour.
"This influx of blood was the starting point for our investigation," Dr Weiss explained. "There is an immunological messenger present during bacterial elicited inflammation that causes this kind of reaction. We searched for it and found it," added the co-author, who is head of the Molecular Immunology group at the HZI.
TNF-alpha is generated by immune cells when Salmonella is recognised. This helps kick-start other immune cells into action. The permeability of the blood vessels increases and TNF-alpha can hone in on the cancerous tissue because the blood vessels in the troubled areas differ fundamentally from healthy arteries or veins: the weak blood vessels are porous and have dead ends.
The researchers said just a tiny amount of TNF-alpha is needed to dissolve the walls of the blood vessels in the tumour and enable the blood to flow into the malignant tissue.
Based on the results of the study, the researchers are seeking to modify Salmonella in order to use it in tumour therapy. The bacteria could migrate into the tumours and trigger their demise. The beauty of Salmonellae is that they are located in various locations of the body that generally are hard to access using common cancer therapies. For example, tissues are not properly supplied with blood, and chemotherapeutics cannot be applied to areas that lack blood flow.
While past research has identified the phenomenon of bacteria attacking tumours, the use of bacteria to treat cancer has never been evaluated because concerns that the patient would die from infection were high. "We have obtained an important indication of how bacteria migrate into tumours," Dr Bartels said. "We can now try to manipulate these bacteria to use them in cancer therapy without causing deadly infections."
Laboratory mice were used in this study, as "it may take years before this method is usable for human patients," Dr Weiss noted.
Due to be completed in 2011, CLINIGENE (European network for the advancement of clinical gene transfer and therapy) is supported by the 'Life sciences, genomics and biotechnology for health' Thematic area of the EU's Sixth Framework Programme (FP6). MIDITRAIN (Molecular interactions during infection), which ended in 2008, was supported under the 'Marie Curie Host Fellowships - Early stage research training (EST)' Mobility scheme of the FP6.
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