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Using Salmonella to Fight Cancer
October 29, 2010   
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Researchers at the Jagiellonian University in Cracow have developed an innovative form of cancer treatment that uses a genetically modified strain of the Salmonella bacterium. Introduced into tumors, the bacterium destroys cancer tissue from the inside.

Tests conducted on animals have proved the efficiency of the therapy. In June, the method was named the Polish Product of the Future in an annual competition held to promote innovative technology.

“The therapy can be classified among immunotherapies, or a group of modern treatment methods that aim to fight cancer by stimulating the body’s own resources,” says Joanna Bereta, Ph.D., from the Jagiellonian University’s Department of Biochemistry, Biophysics and Biotechnology, who is coordinating the project and heads the research team. “Instead of using chemotherapy or radiotherapy, we want to stimulate the patient’s own immune system to fight cancer.”

My enemy’s enemy is my friend

To achieve this goal, the researchers use a natural enemy of humans, the Salmonella bacterium, to fight an even worse enemy—cancer. Naturally, the bacterium used in the therapy had to first undergo appropriate genetic modifications.

The first modification phase equipped the Salmonella bacterium with a fragment of a monoclonal antibody that recognizes specific antigens on the surface of cancer cells. Since the antigens make the cells different from all other cells in the body, the modified bacterium is capable of tracking down the cancer cells and invading tumors.

Another modification weakened the bacterium’s ability to infect people. “Patients who undergo this kind of treatment in the future will not be susceptible to ailments normally caused by Salmonella, as the harmful properties of the bacterium have been radically reduced,” says Paulina Chorobik, a member of Bereta’s research team.

The third and final modification strengthened the bacterium’s cytotoxicity by enhancing its ability to kill cancer cells. The modified Salmonella bacterium easily recognizes cancer tissue and after it is injected into the patient’s bloodstream, it zeroes in on cancer cells, invades the tumor and induces apoptosis, or the process of programmed cell death. At the same time, the patient’s immune system starts producing antibodies against the bacteria located inside the cancer cells.

Preference for colonizing tumors

“This is a totally different and new approach to cancer therapy and we know that the method works on animals,” says Bereta. Tests conducted on mice have shown that the Salmonella bacterium displays a spontaneous preference for colonizing tumors. It thus kills cancer cells and sends signals to the immune system.

The method has not worked in humans so far, but scientists have the tools to make genetic modifications capable of changing that. The next step in the research is to refine the Salmonella strain so that clinical tests on the method can begin. In the future, the new technology can become a new way to treat patients suffering from solid tumors, especially colorectal, lung, breast and stomach cancer and, possibly, other neoplastic diseases such as melanoma.

The researchers at the Jagiellonian University have spent the past four years developing the Salmonella bacterium’s ability to kill cancer cells. Work on this therapy began seven years ago. It was launched by Michał Bereta, Ph.D., from the Department of Immunology at the Jagiellonian University’s Medical College, who was inspired by an American company that planned to devise a therapy employing Salmonella but eventually abandoned the idea. Michał Bereta died in 2008, but his colleagues carried on with the project. The next phase of the research is expected to see the scientists refining the modified strain and starting tests on larger mammals.

Efforts to raise funds for the completion of preclinical tests are being coordinated by the Jagiellonian University Center for Innovation, Technology Transfer and Development (CITTRU). “After the preclinical tests are completed, it will be easier to draw interest from global pharmaceutical corporations,” says Dominik Czaplicki of CITTRU. “We have discussed the technology with companies such as Merck and Roche.”

The center has also applied to patent the technology.

Ewa Dereń
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