Biotechnology: Molecules, Technique and Therapies (Part 2)

by Wiebke Heiss / MEDICA.de15/11/2008

Part 2: Monoclonal antibodies - specific attack on the bad ones


„Please ask your physician or pharmacist about the risks and side effects“ - with the help of something called drug delivery the risks when taking drugs are going to be diminished. Biotechnology is supposed to help in the development of processes that directs medicine to its target where it can unfold its real potential without harming tissues and organs on its way. One big helper in this matter: monoclonal antibodies - immunological proteins that are being produced in the lab and that can find targets extremely specific.

Gerhard Moldenhauer has been developing such molecules for the last 30 years to be used in the diagnosis and therapies of diseases. „The future is going to be very bright. Three to five hundred types of monoclonal antibodies are being investigated in clinical studies at the moment. They are going to flood the market soon," the director of the Department Translational Immunology of the German Cancer Research Center predicts. The goal: Therapies against cancer, rheumatoid arthritis, allergic asthma and more.

When an antigen – a bacterium, a virus or foreign protein – gets into the body cells belonging to the immune system start producing different antibodies that attack the invader at different sites. The total of these different antibodies are called polyclonal. Scientists however want monoclonal antibodies – one and the same type in great numbers. The reason: Monoclonal antibodies made up of just one type identify collectively a predetermined target. A target defined by researchers beforehand.

Hat man seinen bestimmten Typ Antikörper, geht eine Heerschar von ihnen im Körper auf Suche und bindet sich. So können sie zum Beipiel auf Rezeptoren von Wachstumsfaktoren setzen und diese blockieren. „Tumoren werden quasi ausgehungert, da sie nicht mehr zum Teilen angeregt werden können“, sagt Moldenhauer. „Es ist aber auch möglich mit monoklonalen Antikörpern eine antikörperabhängige zellvermittelte Cytotoxizität auszulösen.“ Kurz: Die Antikörper docken an bestimmte Tumormarker und locken natürliche Killerzellen an, die die Geschwulst dann angreifen.

After having developed a specific type of monoclonal antibody, they deploy and search for their bodily target. They can, for example, block receptors for certain growth factors. „Tumours can be starved to death that way since they do not receive the signal to grow anymore," Moldenhauer explains. „It is also possible to initiate an antibody dependent cell cytotoxicity with monoclonal antibodies.“ That means: The immunological active proteins attract natural killer cells after having bound to a tumour.

Antibodies - proteins with potential

However, monoclonal antibodies are also of use in drug delivery: medicine, toxins, radioactive elements can be carried piggyback by the antibodies to a specific target. They dock to certain surface properties of a tumour, the passengers take care of the rest. „A lot of development takes place in this area," Moldenhauer says. The advantages are obvious: Chemotherapy puts a strain on the whole body, whereas monoclonal antibodies ensure that toxins only act on location. „Side effects with monoclonal antibodies are much less when compared to chemotherapy," Moldenhauer says. „Often it is best to use the therapies in combination, though.“

The production of monoclonal antibodies represents an important milestone in biotechnology. The market for these proteins is the fastest growing segment of the pharmaceutical industry. In 2007, more than 26 billion US dollars had been earned with them - mostly in the form of therapies against cancer and autoimmune diseases.

The next milestone is already in sight: „The next breakthrough for monoclonal antibodies will be their use against tumour stem cells," Moldenhauer believes. These cells are the reason why cancer sometimes reappears out of the blue. These cells are the real bad ones and only make up a very small amount of all cancerous cells. They seem to hide somewhere in the body - ready to strike again as researchers have observed with breast and pancreatic cancer: „You need to inject a million normal cancer cells in order to provoke the development of a tumour. With cancer stem cells one percent suffices.“ If it is possible to identify special markers carried by these cancer stem cells it would one day be possible to send out monoclonal antibodies in order to find them in their hiding places.

- Part 1: Molecules, Technique and Therapies
- Part 2: Monoclonal antibodies - specific attack on the bad ones