Playing a Trick on the Immune System

Photo: Pills

Up to now drugs have to trick the
immune system; © SXC

„Give future, donate organs“ – that was the motto of an organ donation day at the beginning of June in Germany. However, the human body is complicated and does not accept present at any cost and may refuse well-meant gifts. As in the case of organ donation. After transplantation the immune system is activated – and it regards the new liver, kidney or lung as an enemy against whom it must fight. A research group around Professor Fred Fändrich of the Clinic for General and Thoracic Surgery at the University Medical Centre of Schleswig-Holstein, has been looking for years for a way to prevent the immune response against the foreign organ in natural manner, almost without drugs. The first results appeared in the journal Transplant International in August 2008.

The idea of the researchers was to mix donor’s cells with those ones of the patient receiving the organ and to inject the mix so that the organ recipient gets used to the foreign cells gently. This is in parts the same principle applied to those suffering from an allergy. The difference: this therapy requires only one treatment. Since 2004, the German researchers have been treating 17 patients with the cell therapy after kidney transplantation. The results appear promising: One patient does not need any more immunosuppressants, all other patients only need a minimum dose of the drugs.

The Essence of the Therapy Are Regulatory Cells

„First, we isolate monocytes from the donor“, Fändrich explains the process. „They are treated with a growth factor and the cytokine gamma interferon. The growth factor stimulates the cells to grow and to divide. The cytokine changes the cell’s surface in a way that they exhibit certain tolerance qualities.“ The monocytes turn into regulatory cells also called transplant-acceptance-inducing-cells (TAIC) and these are then co-cultivated with the recipient’s lymphocytes. „When TAIC are mixed with the lymphocytes, the cells’ surfaces attach to each other giving rise to regulatory t-cells that do not attack foreign donor cells stopping the rejection of a new kidney“,Fändrich says.

The adapted patient’s immune system still recognizes and fights other dangers, though. This is important for fighting cancer cells or other infections which illustrates a big advantage compared to immunosuppressants that cannot differentiate between donor and cancer cells and therefore suppress the immunological reaction against both cell kinds immediately. That results in an increase in the risk of developing tumours or in the failure of fighting bacteria rendering the patient more susceptible for infections. Moreover, the drugs disturb human metabolism resulting in a possible development of diabetes.

Final Results Are Still Missing

However, despite therapy small amounts of drugs are still necessary. All organ recipients in Fändrich’s study received a conventional immunosuppression with three drugs after transplantation. These were considerably reduced after a few weeks only, though. „Generally, the organ recipients still need two drugs one year after transplantation“, says Fändrich. With cell therapy, the intake of cortisone, for example, was stopped after ten weeks. The patients only needed one drug in very small amounts after 24 weeks.

Fändrich stresses that these are only temporary results. „Speaking scientifically, the results are to be considered carefully because we lack a control group“, he explains. This is the next step to be made. „We must find a way not to endanger the patients in the control group.“ It is not ethical to refuse the control group a minimum dose of drugs in turn risking a possible organ rejection. It will take another few years to be certain if cell therapy turns out as a breakthrough in transplantation medicine.

Simone Heimann