What are monoclonal antibodies and what conditions do they treat?

What are monoclonal antibodies? 

During an infection, the human body develops an immune response with the aim of curing the infection by fighting against the invading infectious agent (virus, bacteria, etc.), but also of preventing future infection from this same agent. 

Immune response is a complex set of biological defense reactions, one of which is the production of antibodies. Antibodies, by binding specifically to a particular element of the infectious agent, hinder its action and facilitate its eradication, thus fighting the infection.

Antibodies can also recognize foreign human cells (after a transplant) or mistakenly attack body cells. This is the case in autoimmune diseases such as lupus or multiple sclerosis, for example. 

While the antibodies produced during these events are polyclonal, meaning they recognize various elements of the target cell, monoclonal antibodies, reacting specifically against only one element, are made in a laboratory for medical or scientific use. They are produced by cells in culture: bacteria, yeast, or mammalian cells. These cells have been selected and cultured for their ease of handling and their ability to produce a particular antibody. 

Typically, the monoclonal antibody is produced by immune cells extracted from laboratory animals that have been exposed to the "target protein" (the element that the antibody will recognize). These immune cells are fused with other cells to produce identical strains of cells (cell clones), the most competent of which are selected and cultured to produce a good quality monoclonal antibody on an industrial scale. 

For example, if these immune cells are exposed to a protein necessary for the proliferation of cancer cells, the antibody obtained will bind to this protein, preventing it from fulfilling its role and thus disrupting the growth of the tumor.

Thanks to monoclonal antibodies, it is thus possible to neutralize one protein in an extremely precise manner without affecting the others.

Which conditions do monoclonal antibodies treat? 

In the United States, over 100 monoclonal antibody products are marketed for the treatment of chronic inflammatory conditions, cancers, and for people at high risk of developing severe COVID-19.

Treatment of chronic inflammatory diseases

Chronic inflammatory diseases are conditions in which autoimmunity plays a role. The immune system reacts in an abnormal way and attacks cells in the body that it should not attack. 

This is the case in the following conditions: 

• Rheumatoid arthritis or ankylosing spondylitis: the cells of the joints, ligaments or tendons are attacked. 
• Psoriasis or lupus: the skin cells are attacked. 
• Multiple sclerosis: the nerve fibers are attacked. 
• Crohn's disease or ulcerative colitis: the cells of the intestine are attacked. 

Monoclonal antibodies developed to treat these diseases target the proteins involved in this abnormal immune response. By neutralizing these proteins, it is possible to reduce or even block the autoimmune response that underlies the disease. 

Cancer treatment

In the treatment of cancer, the monoclonal antibodies used have various modes of action. Some are designed to neutralize substances necessary for tumor growth, while others bind to membrane receptors and block the proliferation of cancer cells by disrupting communication between cells. Other monoclonal antibodies prevent the formation of new blood vessels that the tumor needs to grow. 

In addition, an antibody becomes "conjugated" when a chemotherapy molecule is attached to an antibody that recognizes cancer cells. This brings the chemotherapy drug closer to its target, increasing its effectiveness and reducing its side effects. 

Monoclonal antibodies used against cancer can be used alone or in combination with "conventional" chemotherapy drugs. In some cancers, monoclonal antibodies significantly increase the effectiveness of chemotherapy. 

Treatment of adult patients at risk of severe COVID-19

In the US, the FDA has given emergency use authorization (EUA) for certain monoclonal antibodies (casirivimab, imdevimab, bamlanivimab, etesevimab), in a secure setting, to treat adult patients at risk of severe COVID-19 as soon as symptoms appear. 

Monoclonal antibody treatment is available to individuals who:

• Are at high risk for developing severe COVID-19, AND
• Have a positive COVID-19 test and have not yet been admitted to the hospital, AND
• Are 12 years of age or older (and weigh at least 88 pounds)

Post-exposure, preventative monoclonal antibody treatment is available to those who have been exposed to COVID-19 (consistent with the CDC's close contact criteria) and who are:

• At high risk for developing severe COVID-19, AND
• Not fully vaccinated OR vaccinated but immunocompromised, AND
• Are 12 years of age or older (and weigh at least 88 pounds)

How are monoclonal antibodies administered? 

Monoclonal antibodies, if taken orally, would be destroyed by stomach acid. They must therefore be injected under the skin or by intravenous infusion, depending on the treatment, just like biotherapies in general. 

Because of their technical nature and high cost, these treatments are often administered in an outpatient treatment center. 

Monoclonal antibodies warrant close monitoring because they interfere with the immune system and may increase susceptibility to certain illnesses. 

Before prescribing treatment with monoclonal antibodies, the physician must ensure that the patient isn't affected by any infectious diseases. He or she will prescribe the following tests beforehand: a blood test, chest x-ray, screening for tuberculosis and viral hepatitis. A check-up by a dermatologist is also necessary to ensure that there is no risk of skin cancer. 

In addition, the patient must be up to date with his or her vaccinations before starting the treatment. 

With few exceptions, monoclonal antibody treatments should not be administered to pregnant or breastfeeding women. Contraception may be required throughout the course of treatment in women of childbearing age to avoid exposure to the fetus. 

What are the side effects of monoclonal antibodies? 

Long-term side effects differ depending on the nature of the drug, its mechanism of action and the target antigen.

The evaluation of the efficacy and the long-term side effects of monoclonal antibodies is still not well established. 

Side effects and toxicity differ from one drug to another. 

Nevertheless, some studies and post-marketing surveillance have reported the following: 

• Blood disorders: Decrease in the number of one or more types of blood cells, including immune cells
• Recurrent infections: Due to the decrease in the number of immune cells
• Liver problems 
• Kidney problems

However, only the doctor can evaluate the risks and benefits of monoclonal antibody treatments, taking into account several factors such as the severity of the disease and the patient's personal factors (age, history, etc.).

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