Daclizumab

Daclizumab represents a therapeutic monoclonal antibody that acts against the interleukin-2 receptor (CD25). The drug was developed to reduce rejection reactions in kidney transplants. But it has also proven its effectiveness against multiple sclerosis.

What is daclizumab?

Daclizumab is a monoclonal antibody developed for immunosuppression in organ transplants. In particular, the first applications were to reduce rejection reactions in kidney transplants.

The drug is a humanized monoclonal antibody belonging to the IgG1 type. The antibody is produced by murine GS-NSO myeloma cells. The GS-NSO myeloma cells are created by the fusion of B cells with myeloma cells. Myeloma cells are malignant, degenerate immune cells which, after combining with antibody-producing B cells, ensure the permanent cell division and thus new production of the cells.

The resulting cell line constantly produces antibodies that only act against a specific area (epitope) on the surface of the antigen. Initially, the active ingredient daclizumab was developed in the USA at the National Institutes of Health by the company PDL Biopharma. However, it is manufactured and sold by the pharmaceutical company Hoffmann-La Roche under the trade name Zenapax® for the immunosuppressive treatment after a kidney transplant.

PDL Biopharma later formed an alliance with biotechnology company Biogen Idec to further develop daclizumab for the treatment of multiple sclerosis. The results in containing this disease are good. Studies have shown that the neurological situation of the patients has at least stabilized and sometimes even improved.

Pharmacological effect

Daclizumab has immunosuppressive effects. The monoclonal antibodies act against the interleukin-2 receptor (CD25). This receptor serves as a docking point for interleukin-2. Interleukin-2 is a growth factor and stimulates the growth and regeneration of B and T lymphocytes. It also stimulates the formation of interferons, other interleukins and tumor necrosis factors. At the same time, it also activates cytotoxic cells such as natural killer cells, lymphokine-activated killer cells or tumor-destroying lymphocytes.

Finally, it also activates the macrophages. However, interleukin-2 can only fulfill these functions after binding to the interleukin-2 receptors. If the receptor is blocked by the monoclonal antibody, the immune cells can no longer be activated as strongly. The immune system is weakened and with it the rejection reactions against foreign organs. In multiple sclerosis, the autoimmune reaction of the immune system against the medullary sheaths of the central nervous system is inhibited.

Medical application & use

In Europe, daclizumab has been used after kidney transplants as part of combination therapy with corticosteroids and ciclosporin. However, at the request of the manufacturer on 01/01/2009, the approval was withdrawn for commercial reasons. The withdrawal therefore has nothing to do with any side effects.

In addition to its use in kidney transplants, clinical studies have shown good results in heart transplants. It is also used successfully today for uveitis. Uveitis is inflammation of the middle skin of the eye. This disease is an autoimmune reaction against the uvea (middle skin of the eye) after previous infections. The use of monoclonal antibodies against the IL-2 receptor improves the symptoms, since the immunologically induced inflammatory reactions are weakened.

The same mechanism is used to treat multiple sclerosis. In multiple sclerosis, the immune system reacts against the myelin sheaths of the central nervous system. Lesions develop in these myelin sheaths, which in the long term lead to neurological problems. By reducing the inflammatory reactions, such injuries to the medullary sheaths can initially be reversed.

Daclizumab is administered intravenously in both kidney transplants and multiple sclerosis. There are five infusions in total for kidney transplants. The drug is administered intravenously for the first time 24 hours before the transplant. An infusion is then given every 14 days. In the case of multiple sclerosis, according to current studies, two doses initially within two weeks and then one infusion every four weeks is recommended.

Risks & side effects

Daclizumab is absolutely contraindicated in case of hypersensitivity to the active substance and during breastfeeding. Hypersensitivity reactions are very rare. This is anaphylaxis, which can develop into life-threatening anaphylactic shock.

However, more common side effects are headache, insomnia, tremor, arterial hypertension (high blood pressure), breathing problems, various digestive disorders, skeletal muscle pain, and edema.

However, in the studies, daclizumab did not show any effects on the frequency of infections or the frequency of developing cancer. Furthermore, no toxic effects were detected. According to the studies, there is no maximum tolerable dose of the application.