Monoclonal antibodies (MABs)

Content

Introduction

Antibodies (immunoglobulins) are complex molecules produced by B lymphocytes, cells that are part of the human body's defense system (immune system), in response to the presence of another molecule, called antigen, foreign to the organism (for example, bacteria, viruses, etc.).

Sometimes, the immune system mistakenly identifies its normal organs or tissues as foreign and makes antibodies against them (autoantibodies) by attacking them. This process is the cause of autoimmune diseases such as, for example, rheumatoid arthritis and multiple sclerosis.

The antibodies specifically recognize the foreign substance to be fought (antigen) thanks to its conformation and have the task of neutralizing its effect.

Monoclonal antibodies (MABs) are molecules produced in the laboratory, starting from B lymphocytes extracted from the mouse spleen, and fused with blood cancer cells (myeloma cells) which have the characteristic of being immortal. These fused cells, called hybridoma, they are grown individually, in other words they are cloned (one cell in a well). The single cell that has become immortal subsequently divides, forming a clone of identical cells capable of producing unlimited quantities of the same antibody called, in fact, monoclonal which can be purified.Monoclonal antibodies are designed to specifically recognize a single, particular antigen and bind to it by neutralizing it.

There are four types of monoclonal antibodies (MABs):

  • murines (-omab), entirely derived from mouse cells. They can lead to an allergic reaction in humans
  • chimerics (-ximab), obtained using molecular biology techniques that make it possible to replace some parts of the monoclonal antibody derived from mouse cells (the constant region) with the corresponding part of protein of human origin. They can cause allergy
  • humanized (-zumab), derived mainly from human cells with the exception of the part of the antibody that binds to the target antigen
  • humans (-umab), entirely derived from human cells

MABs can be produced in large quantities against antigens from a range of inflammatory diseases, infections and cancers and are used for both diagnostic and therapeutic purposes. In addition, they are also used to enhance the body's natural defenses.

MABs can be linked (conjugated) to drugs or radioactive molecules (radioimmunotherapy) to convey and direct the active ingredient towards its target with extreme precision. In this way we avoid involving other parts of the body, reducing unwanted effects and increasing the chances of efficacy of the therapy. Radioimmunotherapy is a technique that is mainly applied in the treatment of tumors.

Monoclonal antibodies in diagnostics

Monoclonal antibodies can also be used to determine the presence (diagnose) of a specific antigen and possibly measure its quantity. They are therefore used to identify antigens of infectious agents, such as viruses and bacteria, as well as specific proteins and antigens present on tumor cells (tumor markers).

Monoclonal antibodies can also be used in home diagnostic kits such as pregnancy tests.

Monoclonal antibodies in therapy

Monoclonal antibodies used in therapy (treatment) can be divided according to their activity:

  • anti-inflammatory
  • immunosuppressive
  • antitumor

The monoclonal antibody affects and interferes with the action of a chemical or receptor involved in the development of the disease to be treated.

Monoclonal antibodies (MAB) with anti-inflammatory activity

These MABs exert an anti-inflammatory action because their target antigen is made up of substances involved in inflammation such as, for example, TNF-α.
TNF-α (tumor necrosis factor alpha) is involved in the onset of all disorders (symptoms) found in inflammatory diseases on an autoimmune basis such as, for example, rheumatoid arthritis and psoriatic arthritis. Infliximab and adalimumab belong to this group of drugs.

Monoclonal antibodies (MAB, monoclonal antibodies) with immunosuppressive activity

They have the task of suppressing the body's immune defenses. These MABs, in fact, are aimed above all against immune cells, B lymphocytes and T lymphocytes, and against the fundamental proteins for their differentiation and activation such as, for example, the "interleukin-2.
They are used in the treatment of autoimmune diseases and in the prevention of rejection of transplanted organs. Rituximab (also used in the treatment of some types of lymphomas), basiliximab and also omalizumab, used in the treatment of allergic asthma, belong to this group of drugs.

Monoclonal antibodies (MAB) with antitumor activity

These monoclonal antibodies recognize and bind to factors essential for the development of cancer cells or to antigens deriving from certain types of tumors such as, for example, HER-2, in breast tumors.Trastuzumab, rituximab, cetuximab and bevacizumab and many others belong to this group of MABs. MABs with antitumor activity are also those directed against the "immunological check-points" that are used in immunotherapy.

Cancer cells can avoid being recognized by the immune system or block the activity of the immune system itself. Some specific MABs have the ability to activate the body's defense system response (immune response) against tumors in several ways. :

  • signaling the presence of cancer cells, MAB-coated cancer cells can be more easily discovered and destroyed by the immune system
  • activating the destruction of the cell membrane, some MABs can trigger an immune system response that can destroy the membrane of cancer cells
  • blocking cell growth, some monoclonal antibodies block the growth of cancer cells
  • preventing the growth of blood vessels, for a tumor to grow, and survive, it must be fed. Some MABs block the interaction between cells and the proteins necessary for the development of new blood vessels
  • blocking immune system inhibitors, some proteins that bind to cells of the immune system regulate the activity of the system itself. MABs bind to these proteins blocking the inhibition of the immune system and promoting activity against cancer cells
  • directly attacking cancer cells, some MABs can directly attack the cancer cell by activating a series of events inside the cell itself that lead to its self-destruction
  • carrying radioactive isotopesDue to its high affinity characteristics, a monoclonal antibody can be designed as a transport medium for other therapies.When a monoclonal antibody is bound to a radioactive particle, it transports it directly to the target tumor cells thus minimizing the effect of radiation on healthy cells. This variation of traditional radiotherapy is called radioimmunotherapy
  • delivering chemotherapy drugs, some MABs are linked to a chemotherapy drug to transport it directly to cancer cells avoiding the destructive effect on healthy cells
  • by binding to cancer cells and immune cells, some therapies use the combination of two monoclonal antibodies, one targeting the cancer cell and one targeting a specific immune system cell. This combination can increase the efficiency of the immune system's attack on cancer cells

Monoclonal antibody therapies have been approved for some cancers including:

  • chronic lymphocytic leukemia
  • Hodgkin's lymphoma
  • non-Hodgkin's lymphoma
  • melanoma
  • brain cancer
  • breast cancer
  • colorectal cancer
  • lung cancer
  • prostate cancer
  • stomach cancer

Monoclonal antibodies (MABs) are administered intravenously. Some MABs can be used in conjunction with chemotherapy or hormone treatments. Others are still being tested and used only when other treatments have not been successful.

In general, monoclonal antibody therapy has fewer unwanted effects (side effects) than traditional chemotherapy treatments, although some can also be serious.

It is up to the doctor to explain what side effects are associated with that particular drug.

Common side effects

In general, the most common side effects (side effects) caused by MABs include:

  • allergic reactions, such as hives or itching
  • flu-like signs and symptoms, including chills, fatigue, fever, and body aches
  • nausea
  • diarrhea
  • skin rashes
  • low blood pressure

Serious side effects

Serious, but rare, side effects of monoclonal antibody therapy can include:

  • reactions to the infusion, severe allergic reactions can occur. Reactions to the infusion usually occur during the administration of therapy or soon after, so while the person is still under medical supervision
  • anemia, MABs linked to radioactive particles or chemotherapy drugs can lead to a decrease, even severe and persistent, in the number of red blood cells
  • heart problems, some MABs increase the risk of hypertension, heart failure, and heart attacks
  • lung problems, some MABs are associated with an increased risk of lung inflammation
  • skin problems, in some cases the wounds and rashes can lead to serious infections. Severe injuries can also occur on the tissue that lines the cheeks and gums (mucous membrane)
  • bleeding, MABs designed to inhibit the formation of new blood vessels increase the risk of internal bleeding

The risk-benefit ratio of each therapy and the opportunity to undergo it must be discussed with your doctor.

Bibliography

Mayo Clinic. Monoclonal antibody drugs for cancer: How they work (English)

In-depth link

Medicine Net. Monoclonal Antibodies (English)

National Institute for Cellular Biotechnology (NICB). What is a monoclonal antibody? (English)

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