Alemtuzumab

The monoclonal antibody Alemtuzumab binds to certain white blood cells (B and T lymphocytes) and causes them to break down. While alemtuzumab was previously approved for chronic lymphocytic leukemia (CLL), it is now mainly used for multiple sclerosis (MS).

What is alemtuzumab?

Alemtuzumab is a monoclonal antibody that specifically binds to the CD52 antigen on the surface of lymphocytes. If the human body forms antibodies as a natural reaction to contact with pathogens, then these are always polyclonal.

This means that the antibodies formed come from many different cells and are directed against different epitopes (binding sites for antibodies). In contrast, monoclonal antibodies are genetically engineered. They are produced in the laboratory by cells from a specific cell line.

These cell clones all form exactly the same (monoclonal) antibody, which is directed against 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.

Pharmacological effect

Lymphocytes are part of the immune system and belong to the white blood cells. Antibodies with a specificity against lymphocytes recognize them and bind specifically to a certain antigen on this cell type. By binding the antibody, the body's own 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 given to patients as an infusion under medical supervision. The preparation 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 abnormally changed. However, the lymphocytes are part of the natural immune system. A breakdown of these cells always leads to a weakening of the immune system.

Medical application & use

The monoclonal antibody altemtuzumab was used against chronic lymphocytic leukemia (CLL) under the trade name MabCampath®. In this disease it was shown to be effective as cancer immunotherapy in some of the patients.

In the meantime, however, the approval of alemtuzumab for the indication CLL has been withdrawn by the manufacturer. The background for this was obviously commercial considerations and no undesirable drug effects (side effects). In 2013, alemtuzumab was re-approved for the treatment of multiple sclerosis (MS) and re-launched under the trade name Lemtrada® - but 40 times more expensive than the previous preparation.

Today, alemtuzumab is therefore mostly used in multiple sclerosis (MS). The aim 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. The body then forms new B and T lymphocytes again. Alemtuzumab can therefore be dosed significantly lower in MS than in cancer therapy.

Outside of approval, alemtuzumab continues to be used in certain subsets of CLL patients and is used in induction therapy for kidney transplants.

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Risks & side effects

The most common side effects of the antibody alemtuzumab are rashes, headache, fever, and respiratory infections. Many of the undesirable effects are based directly on the lymphocyte-killing effect. In this way, a suppression of the immune system is achieved, which is sometimes also 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 worsen autoimmune diseases. Idiopathic thrombocytopenic purpura (ITP) occurred in individual cases after treatment with alemtuzumab. ITP is also called immune thrombocytopenia and is an autoimmune disease that affects the blood platelets (thrombocytes).

One in four MS patients treated developed autoimmune reactions to the thyroid gland. These led in part to Graves' disease, an overactive thyroid disease. In order to detect such serious side effects, the patient's blood count will be monitored closely during treatment.