The monoclonal antibody alemtuzumab binds to certain white blood cells (B and T lymphocytes) and causes them to break down. While alemtuzumab was also previously approved for chronic lymphocytic leukemia (CLL), it is now mainly used for multiple sclerosis (MS).
What is alemtuzumab?
While alemtuzumab was also previously approved for chronic lymphocytic leukemia (CLL), it is now mainly used for multiple sclerosis (MS). Alemtuzumab is a monoclonal antibody that specifically binds to the antigen CD52 on the surface of lymphocytes. If the human body forms antibodies as a natural reaction to contact with pathogens, these are always polyclonal. This means that the antibodies formed originate from many different cells and are directed against different epitopes (binding sites for antibodies). Monoclonal antibodies, on the other hand, are produced by genetic engineering. They are produced in the laboratory from cells of a specific cell line. These cell clones all form the exact same (monoclonal) antibody, which is directed against only a single, specific epitope. In the case of alemtuzumab, this is the surface antigen CD52, which is found on healthy and malignant B and T lymphocytes.
Pharmacologic action
Lymphocytes are part of the immune system and belong to the white blood cells. Antibodies with specificity against lymphocytes recognize them and bind specifically to a particular antigen on that cell type. As a result of the binding of the antibody, the body’s immune system recognizes the lymphocytes and breaks them down. An example of a lymphocyte-specific antibody is alemtuzumab. This antibody is directed against CD52. CD52 is also known as the CAMPATH1 antigen and is found almost exclusively on mature lymphocytes. CD52 is found on both B lymphocytes (B cells) and T lymphocytes (T cells). For treatment, alemtuzumab is administered to patients as an infusion under medical supervision. The drug selectively kills the lymphocytes in the patient’s body. Depending on the dosage, the drug is suitable for reducing the number of lymphocytes to a greater or lesser extent. This can be important, for example, in diseases in which the lymphocytes are pathologically altered. However, lymphocytes are part of the natural immune system. A reduction in these cells always leads to a weakening of the immune defenses as well.
Medical application and use
Under the trade name MabCampath, the monoclonal antibody altemtuzumab has been used against chronic lymphocytic leukemia (CLL). In this disease, it showed good efficacy as a cancer immunotherapy in a proportion of patients. In the meantime, however, the approval of alemtuzumab in the indication CLL has been withdrawn by the manufacturing company. The background for this was apparently commercial considerations and no adverse drug reactions (side effects). In 2013, alemtuzumab was re-approved for the treatment of multiple sclerosis (MS) and relaunched on the market under the trade name Lemtrada – albeit 40 times more expensive than the previous preparation. Today, alemtuzumab is therefore largely used in multiple sclerosis (MS). The goal is not to kill as many lymphocytes as possible, but only to temporarily decimate the immune cells. In MS, these are involved in the destruction of the myelin sheaths in the central nervous system. Subsequently, the body forms new B and T lymphocytes again. Alemtuzumab can therefore be dosed much lower in MS than in cancer therapy. Off-label, alemtuzumab continues to be used in certain subsets of CLL patients and is used in induction therapy for kidney transplantation.
Risks and Side Effects
The most common side effects of the antibody alemtuzumab are skin rashes, headache, fever, and respiratory infections. Many of the adverse effects are directly due to the lymphocyte-killing effect. This results in suppression of the immune system, which is sometimes desirable (for example, in the treatment of patients with multiple sclerosis). At the same time, however, a weakened immune system always increases the risk of infections and can trigger or intensify autoimmune diseases. In individual cases, idiopathic thrombocytopenic purpura (ITP) occurred after treatment with alemtuzumab. ITP is also called immune thrombocytopenia and is an autoimmune disease that affects the blood platelets (thrombocytes).Autoimmune reactions against the thyroid gland occurred in every fourth MS patient treated. In some cases, these led to Graves’ disease, an overactive thyroid gland. To detect such serious side effects, patients’ blood counts are closely monitored during treatment.
