Monoclonal Antibodies

An antibody is a protein produced by the body's immune system in response to antigens, which are harmful substances. Antigens include bacteria, fungi, parasites, viruses, chemicals, and other substances the immune system identifies as foreign.

Sometimes the body mistakenly identifies normal tissues as foreign and produces antibodies against the tissue. This is the underlying cause of autoimmune conditions such as rheumatoid arthritis and multiple sclerosis or MS.

Antibodies are naturally produced by the immune system. However, scientists can produce antibodies in the lab that mimic the action of the immune system. These man-made (synthetic) antibodies act against proteins that attack normal tissues in people with autoimmune disorders. Man-made antibodies are produced by introducing human genes that produce antibodies into mice or another suitable mammal.

The mice then are vaccinated with the antigen that scientists want to produce antibodies against. This causes the immune cells of the mice to produce the desired human antibody. The term monoclonal antibody means that the man-made antibody is synthesized from cloned immune cells, and the identical monoclonal antibody produced binds to one type of antigen. Polyclonal antibodies are synthesized from different immune cells and the antibodies produced bind to multiple antigens.

In recent years, monoclonal antibody therapy has been studied and then given emergency use authorization (EUA) for the treatment of the coronavirus disease COVID-19. 

The use of monoclonal antibodies to treat diseases is called immunotherapy therapy because each type of monoclonal antibody will target a specific targeted antigen in the body.

Uses for monoclonal antibodies include:

• Cancer
• Rheumatoid arthritis
• Multiple sclerosis
• Cardiovascular disease
• Systemic lupus erythematosus
• Crohn's disease
• Ulcerative colitis
• Psoriasis
• COVID-19
• Transplant rejection, and several more conditions

In these conditions the monoclonal antibody targets and interferes with the action of a chemical or receptor that is involved in the development of the condition that is being treated. For example, a monoclonal antibody used for treating cancer may block a receptor that cancer cells use for preventing the immune system from destroying the cancer cell. Blocking this receptor allows the immune system to recognize cancer cells and destroy them.

Monoclonal antibodies are designed to be administered by injection. They are supplied as:

• Lyophilized powder for reconstitution
• Solution for injection

Monoclonal antibody treatments are allowed by the FDA under an emergency use authorization (EUA) for COVID-19. The only two currently authorized monoclonal antibody medications for COVID-19 include bebtelovimab and tixagevimab/cilgavimab. 

• Bebtelovimab is authorized to treat outpatients only and not patients who have been admitted to the hospital with serious symptoms of COVID-19 and require oxygen therapy.
• Evusheld (tixagevimab/cilgavimab) is to prevent or protect someone from becoming ill before they are exposed to COVID-19. It is not used to treat COVID symptoms or prevent someone from illness after being exposed to the virus. Evusheld is not a substitute for COVID vaccination.

The following drugs have been paused from production in the United States because they are not expected to provide protection against the Omicron variant of COVID-19:

• Bamlanivimab plus etesevimab
• Casirivimab plus imdevimab
• Sotrovimab 

Clinical studies continue to study the usefulness and safety of the above COVID-19 antibody treatments.

Here is a list of examples some FDA-approved monoclonal antibody drugs.

• abciximab (Reopro)
• adalimumab (Humira, Amjevita)
• alefacept (Amevive)
• alemtuzumab (Campath)
• basiliximab (Simulect)
• belimumab (Benlysta)
• bezlotoxumab (Zinplava)
• canakinumab (Ilaris)
• certolizumab pegol (Cimzia)
• cetuximab (Erbitux)
• daclizumab (Zenapax, Zinbryta)
• denosumab (Prolia, Xgeva)
• efalizumab (Raptiva)
• golimumab (Simponi, Simponi Aria)
• inflectra (Remicade)
• ipilimumab (Yervoy)
• ixekizumab (Taltz)
• natalizumab (Tysabri)
• nivolumab (Opdivo)
• olaratumab (Lartruvo)
• omalizumab (Xolair)
• palivizumab (Synagis)
• panitumumab (Vectibix)
• pembrolizumab (Keytruda)
• rituximab (Rituxan)
• tocilizumab (Actemra)
• trastuzumab (Herceptin)
• secukinumab (Cosentyx)
• ustekinumab (Stelara)

Each monoclonal antibody listed above has a role in treating a targeted disease (for example, basiliximab treats transplant rejection while belimumab treats systemic lupus erythematosus).

These side effects are compiled from side effects listed for several monoclonal antibodies. Each type of monoclonal antibody has its own side effect profile and may or may not cause some of the side effects listed here.

Common side effects of monoclonal antibodies include:

• Allergic reactions
• Chills
• Weakness
• Diarrhea
• Nausea
• Vomiting
• Rash
• Itching
• High blood glucose levels
• Cough
• Constipation

Other side effects of monoclonal antibodies include:

• Shortness of breath
• Peripheral edema
• Headache
• Fever
• Muscle aches and pain
• Decreased appetite
• Increased triglyceride levels
• Insomnia
• Abdominal pain
• Back pain
• Dizziness

Serious side effects of monoclonal antibodies may include one or more of the following:

• Low blood pressure
• Anaphylaxis
• Serious infections
• Cancer
• Serum sickness
• Autoimmune thyroiditis
• Arterial and venous blood clots
• Congestive heart failure
• Bleeding
• Interstitial lung disease
• Hepatitis
• Generation of antibodies
• Enterocolitis
• Gastrointestinal perforation
• Mucositis
• Stomatitis
• Anemia
• Reduced white blood cell counts
• Hypothyroidism

• Serious infections are more likely to occur when monoclonal antibodies are combined with other drugs that suppress the immune system (for example, steroids).
• Another example of drug interaction is that the drug methotrexate reduces the absorption of adalimumab (monoclonal antibody) by 29%-49%, but no adjustments to the dose of adalimumab need to be made when methotrexate is given concomitantly.
• Monoclonal antibodies may interfere with the effectiveness of vaccines. Live vaccines, including attenuated vaccines, should not be used while patients are being treated with monoclonal antibodies. Patients should complete all recommended immunizations prior to receiving monoclonal antibodies.

Pregnancy

• Monoclonal antibodies have not been adequately studied in pregnant women or women who are breastfeeding. Some monoclonal antibodies, for example, nivolumab (Opdivo) and pembrolizumab (Keytruda), may be harmful to the fetus because of their mechanism of action and from other results obtained from animal studies.

Breastfeeding

• It is not known whether monoclonal antibodies are present in breast milk. Mothers who are breastfeeding should decide whether to stop or discontinue the monoclonal antibody because many drugs, including large proteins like monoclonal antibodies, are excreted in breast milk and there is a risk of serious adverse effects in the infant.