Blog 10: Monoclonal Antibodies

Monoclonal antibodies are a form of treatment options for individuals suffering from autoimmune diseases, cancer, or allergies, among other things. They are unique to other antibody treatments in that all the antibodies given to the patient are specific (Textbook) to one epitope on one antigen. Normally, antibody treatments may be specific to an antigen but are not specific to an epitope on that antigen. This allows for greater specificity in whatever disease you are trying to target. Monoclonal antibodies are created in an animal vessel. The animal is injected with the specific antigen researchers are trying to treat so that the animal will make antibodies to it. B cells produced by the animal are isolated and mixed with a form of cancer cell, known as a myeloma cell. These are important because they allow for uncontrolled cell growth and are susceptible to aminopterin, an immunosuppressive drug. The two cells are mixed and incubated on a plate containing aminopterin, forcing the cells to fuse together and become hybridoma cells. The hybridoma cells combine the wanted traits from both cells; the B cell provides the genes necessary for antibody production, while the myeloma cells provide the mechanism for uncontrolled cell growth.

One type of monoclonal antibody, omalizumab, is given to patients who suffer moderate to severe asthma. Asthma, which is a Type 1 hypersensitivity reaction (Textbook), involves spasms of the muscles that line the bronchial tubes and an increase in mucous production. Type 1 hypersensitivity reactions are characterized by IgE antibodies bound to Fc receptors on mast cells or basophils. When these antibodies recognize their specific antigen, they bind the antigen and the mast cells will degranulate, releasing chemicals that induce inflammation. When this type of reaction occurs in the lower respiratory tract, muscle spasms occur, causing the known signs and symptoms of asthma. Omalizumab helps to prevent this reaction by binding to free IgE antibodies, which keeps them from binding to the Fc receptors on basophils and mast cells. As they are bound to an antibody, IgE can not induce the mast cells to degranulate, reducing the number of asthma attacks affected individuals experience. Numerous clinical studies also seem to suggest that a decrease in the amount of free IgE antibodies causes downregulation of IgE Fc receptors on basophils, further preventing future attacks. However, this treatment is meant to be an additional form of therapy for asthma patients, as it is not intended to treat attacks while they are happening, so corticosteroid inhalers are still recommended for use in combination with omalizumab.

As with any immunosuppressive drugs, there are a few serious side effects associated with omalizumab. More serious, but rare side effects include cancer, inflammation of the blood vessels, parasitic infections, and heart and circulation problems. Omalizumab works by binding to IgE, preventing it from exerting its effects. While this is helpful in preventing asthma attacks, it also puts the patient at an increased risk of developing a parasitic infection, as IgE’s main function is to destroy parasitic worms. If the patient lives in an area where parasitic worms are common, the patient should be closely monitored. In a study to see how omalizumab is associated with cancer, researchers found that 0.5% of the participants who were taking omalizumab developed cancer, compared to the 0.2% that were taking a placebo. Researchers explained that the relationship is most likely not causal, especially since the participants developed different types of cancers. However, they did suggest that further research should still be done before a conclusion can be made concerning omalizumab and cancer. Other more common side effects for patients over 12 include leg and arm pain, dizziness, fatigue, skin rash, bone fractures, and ear pain. One other problem that occurs in a very small percentage of patients (less than 0.1%) but needs to be recognized, is anaphylactic shock upon receiving the injection of omalizumab. Because of this, patients are required to be monitored 2 hours after the injection, as this is when anaphylaxis shock is most likely to occur. However, it can still happen up to 24 hours after the injection, so patients might be given epinephrine pens in case this happens.

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