Daclizumab represents a therapeutic monoclonal antibody that targets the interleukin-2 receptor (CD25). The drug was developed to reduce rejection in kidney transplantation. However, it has also demonstrated efficacy against multiple sclerosis.
What is daclizumab?
The drug was developed to reduce rejection in kidney transplantation. Daclizumab is a monoclonal antibody developed for immunosuppression in organ transplantation. In particular, the first applications were for the reduction of rejection in kidney transplantation. The drug represents a humanized monoclonal antibody belonging to the IgG1 type. The antibody is produced by murine GS-NSO myeloma cells. GS-NSO myeloma cells are generated by the fusion of B cells with myeloma cells. Myeloma cells are malignant, degenerate immune cells that, after fusion with antibody-producing B cells, provide for continuous cell division and thus new cell production. The resulting cell line constantly produces antibodies that act only 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 marketed by the pharmaceutical company Hoffmann-La Roche under the trade name Zenapax for immunosuppressive treatment after kidney transplantation. Later, PDL Biopharma formed an alliance with biotechnology companies Biogen Idec and further developed daclizumab for the treatment of multiple sclerosis. Success in curbing this disease has been good. Studies have shown that the neurological situation of patients has at least stabilized and sometimes even improved.
Pharmacologic effect
Daclizumab has immunosuppressive effects. The monoclonal antibodies act against the interleukin-2 receptor (CD25). This receptor serves as a docking site for interleukin-2. Interleukin-2 is a growth factor and stimulates the growth and new formation of B and T lymphocytes. Furthermore, it 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 ensures the activation of macrophages. However, interleukin-2 can only perform these functions after binding to 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, in turn, the immune system‘s autoimmune reaction against the myelin sheaths of the central nervous system is inhibited.
Medical application and use
In Europe, daclizumab has been used for use after renal transplantation as part of combination therapy with corticosteroids and ciclosporin. However, the approval was withdrawn at the request of the manufacturer on 01.01.2009 for commercial reasons. The withdrawal has therefore nothing to do with possible side effects. In addition to its use in kidney transplantation, clinical studies have also shown good results in heart transplantation. Furthermore, it is now also used successfully in uveitis. Uveitis is an inflammation of the middle skin of the eye. This disease is an autoimmune reaction against the uvea (middle eye skin) after previous infections. By using the monoclonal antibodies against the IL-2 receptor, improvements in symptoms occur as the immunologically induced inflammatory reactions are attenuated. Multiple sclerosis is also treated by the same mechanism. In multiple sclerosis, the immune system reacts against the myelin sheaths of the central nervous system. Lesions occur in these myelin sheaths, leading to neurological problems in the long term. By reducing the inflammatory reactions, such lesions of the myelin sheaths can also be initially reversed. In both kidney transplants and multiple sclerosis, daclizumab is administered intravenously. For kidney transplants, there are a total of five infusions. Thus, the drug is first administered intravenously 24 hours before the transplant. Thereafter, an infusion is given every 14 days.In multiple sclerosis, current studies recommend two infusions within two weeks initially and one infusion every four weeks thereafter.
Risks and side effects
Daclizumab is absolutely contraindicated in hypersensitivity to the active ingredient and during breastfeeding. Hypersensitivity reactions occur very rarely. These involve anaphylaxis, which can also progress to life-threatening anaphylactic shock. However, more common side effects include headache, insomnia, tremor, arterial hypertension (high blood pressure), breathing problems, various digestive disorders, skeletal muscle pain, and edema. However, daclizumab has not shown any effects on the incidence of infections or the incidence of developing cancer in the studies. Furthermore, no toxic effects have been demonstrated. Thus, according to the studies, there is no maximum tolerable dose of use.
