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Training our sights on cancer cells
Regular examinations confirm to Theo Krupatz and his doctor, Klaus Struck, that the chemotherapy was successful. His lungs are now normal.
Trojan horse: In the development of new medicines, Bayer HealthCare harks back to a successful war stratagem from antiquity. Just as Greek soldiers once gained entry to the city of Troy concealed inside the belly of a wooden horse, today’s researchers are concealing active ingredients in novel antibodies and sending them through the body undetected to be delivered into the cancer cell, where they embark on their work of destruction in a specific and targeted manner.
Four billion white blood cells per liter of blood – this is the minimum people need to fight off disease pathogens effectively. When Theo Krupatz was admitted to hospital in August 2007 with a slight fever, his blood contained only a fifth of this amount. His doctors did not have to search long for the cause of this drastic reduction in his white blood cell count. It was clearly the result of chemotherapy.
Eight weeks previously, Krupatz had had his “life shaken.” The diagnosis: lung cancer. “Fortunately, the cancer had not yet spread,” explains the 74-year-old man. The doctors removed part of his left lung and advised him to have chemotherapy to kill off any remaining cancer cells in his body. Krupatz knew to expect side effects. The powerfully built man lost weight, his hair fell out, he was constantly tired. “But you put up with it if it increases your chances of beating the cancer,” he says in retrospect. Millions of people go through this experience each year. In Germany alone, there are around 500,000 new cases of cancer per year according to statistics. Many of these patients receive chemotherapy, a treatment involving potent drugs, also known as cytostatic agents, which interfere with cell division and thus counteract tumor growth. Individual cancer cells remaining after surgery can be killed off by this treatment. If metastases have formed, cytostatic agents can at least slow progression and thereby help to prolong the patient’s life.
Zoom imageClose-up: Tumor cells divide rapidly and unchecked. The photo shows a lung cancer cell during cell division – taken with a scanning electron microscope.
Side effects of chemotherapy
But cytostatic agents often have significant side effects which can even lead to the treatment being stopped. This is because, as well as hair loss and nausea, they can cause severe inflammation of the mucous membranes or, as in the case of Theo Krupatz, a drastic reduction in the number of blood cells. The reason for this is that “chemotherapeutic agents also attack healthy cells, because traditional cytostatic agents are not specific. In other words, they don’t just affect cancer cells,” says Dr. Holger Hess-Stumpp, a cancer research biologist at Bayer HealthCare. Krupatz was lucky: his blood counts soon stabilized, and the chemotherapy was continued at a lower dose. The pensioner is now living his life almost free from symptoms, and the results of the regular follow-up examinations of his lungs have remained normal.
Cancer cells have a survival strategy
Side effects are just one of the limitations of treatment with cytostatic agents. These agents have little or no effect in certain types of cancer, for example. Another problem is the development of resistance. “Cancer cells have all sorts of survival strategies which lead to them becoming insensitive to the drugs used against them,” explains Hess-Stumpp. A major challenge for the Bayer HealthCare researchers, who are working on innovative drugs in order to target cancer more specifically while broadening the repertoire of effective anti-cancer drugs. The aim is to develop new therapies which combine high efficacy with acceptable side effects to enable cancer patients to be treated for the maximum length of time and thus to prolong their lives significantly.
Biologicals research: Dr. Heiner Apeler and Dr. Holger Hess-Stumpp in front of the plant in which antibodies are separated from other proteins.
One of the ways researchers hope to achieve this is with novel active ingredients which are biopharmaceutically based – particularly tailor-made antibodies. A license from German biotech company MorphoSys has enabled them to identify the basic structure of suitable antibodies. These therapeutic proteins are able to knock out cancer cells in a targeted manner. The proteins developed by the Bayer researchers are designed to dock with specific structures on the surface of cancer cells as accurately as antibodies produced by the body in response to infections bind to disease pathogens.
“Antibodies are a perfect complement to chemically produced active ingredients. They enable us to target sites which cannot be reached with small chemical molecules,” explains researcher Dr. Heiner Apeler, a biologist on the team of pharmaceutical research scientists at Bayer HealthCare that is working on the development of antibodies and other biopharmaceutical active ingredients.
They identify typical target sites for cancer cells, develop antibody structures with an affinity for these sites from a range of options using a complicated process and then apply the necessary finishing touches. Depending on target site and antibody design, the innovative active ingredients are finally able to attack the tumor in a variety of ways.
Antigens as an effective means of transport
For example, Bayer researchers are working on antibodies which block important signaling pathways and thus cut off the supply of nutrients to the tumor. Others might prevent interactions with adjacent tissues and thus inhibit the formation of blood vessels within the tumor, for example. Yet others may have the ability to attract “killer cells” in the body which then destroy the cancer cells.
Antibody conjugates could be another powerful weapon against cancer. With this approach, researchers make use of the highly specific nature of antibodies in order to transport a chemotherapeutic agent directly into tumor cells. Biologists and chemists work hand in hand in developing such conjugates. The biologist develops a specific antibody which is tailored exactly to defined structures on the surface of certain cancer cells. The chemist is responsible for linking a potent cytotoxin firmly to the antibody.
Inside the body, the combination remains intact initially on its journey through the bloodstream to the tumor. Here, it docks to the surface of the cell using its antibody structures, after which it is internalized completely into the cancer cell. Once inside, substances already present in the cell bring about separation. The antibody has done its job and the released toxin can set about destroying the tumor cell. The critical advantage of the process is that healthy cells are likely to be left largely unscathed because the antibody is able to find few if any docking sites on these cells. “Based on these conditions we hope to be able to use very potent chemotherapeutic agents which accumulate in the cancer cell in high concentrations. This might provide an extremely effective means of combating the tumor,” is the way Hess-Stumpp sums up the expectations for these powerful combinations.