What Is a Monoclonal Antibody?

A Manufactured Immune Protein Used to Diagnose and Treat Diseases

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A monoclonal antibody (mAb) is a type of immune protein produced in a lab that binds to a specific protein on a cell called an antigen. As with naturally occurring antibodies, monoclonal antibodies stimulate the immune system to act against disease-causing agents.

Matching a specific human-made antibody to a particular target has many applications in medicine. This includes the targeted treatment of diseases like cancer, rheumatoid arthritis, and COVID-19. Monoclonal antibodies can also be used to type blood samples, detect pregnancy, and diagnose infectious and noninfectious diseases.

This article explains how monoclonal antibodies are created and used in medicine. It also describes the risks and benefits of monoclonal antibody therapies that are approved in the United States.

Healthcare provider adjusting intravenous infusion for person in clinic

Space_Cat / Getty Images

How Monoclonal Antibodies Work

Antibodies (Ab) are proteins produced by specialized white blood cells—called B cells—which the immune system uses to identify and neutralize foreign agents like viruses, bacteria, and cancer. Each antibody is matched to the unique antigen on the surface of the invader.

Monoclonal antibodies are designed to mimic the action of naturally occurring antibodies. The term "monoclonal" refers to the process of creating an exact copy (a clone) of cells that produce antibodies.

There are several ways to produce monoclonal antibodies, but they traditionally involve exposing a mouse to a disease-causing agent like a virus or cancer. The animal's B cells are then harvested, manipulated, and cloned to mass-produce antibodies specific to the disease-causing agent.

The animal-derived antibodies can then be further manipulated to prevent the immune system from regarding them as foreign invaders and attacking them. This may involve fusing or grafting mouse antibodies onto human antibodies.

Types of Monoclonal Antibody

The four categories of monoclonal antibodies classified by the amount of mouse antibodies and human antibodies in them are:

  • Murine monoclonal antibodies consist of 100% mouse antibodies.
  • Chimeric monoclonal antibodies consist of more than 65% human antibodies and are made by fusing mouse antibodies with human antibodies.
  • Humanized monoclonal antibodies consist of more than 90% human antibodies and are made by grafting parts of mouse antibodies onto human antibodies.
  • Human monoclonal antibodies consist of 100% human antibodies and are made by inserting the genetic material of mouse antibodies into human antibodies.

Monoclonal antibodies can also be produced using recombinant DNA technology, in which the genetic material of an antibody is transferred to a host cell (such as yeast, bacteria, or mammalian tissue) capable of churning out mass quantities of the antibody. Unlike the traditional method of mAb production, however, recombinant antibodies are made entirely in the lab or production facility without animals.

History

The first therapeutic monoclonal antibody was created in 1975, and the first licensed monoclonal antibody, called Orthoclone OKT3 (muromonab-CD3), was approved by the Food and Drug Administration (FDA) in 1986.

Diagnostic Uses of Monoclonal Antibodies

One of the earliest applications of monoclonal antibodies was their use in diagnosing medical conditions. Monoclonal antibodies function in the same way as naturally occurring antibodies in that they "recognize" foreign agents. By doing so, they can detect not only disease but important variations in normal cells (such as blood cells) and abnormal cells (such as cancer).

One of the first applications of monoclonal antibodies was in blood typing and tissue typing (used to prevent organ transplant rejection). In both cases, the tests ensure a "match" between a blood or tissue donor and a blood or tissue recipient.

Monoclonal antibodies are also used to identify infectious and noninfectious diseases. Because they are highly specific, monoclonal antibodies offer a high degree of accuracy when used in blood, urine, and tissue tests.

This includes the Western blot used to diagnose diseases based on specific proteins in a blood or tissue sample. A positive result is returned when the introduced antibody binds to its target antigen in the sample.

The Western blot can diagnose several common and uncommon diseases, including:

Monoclonal antibodies can also be applied to a technique called immunohistochemistry (IHC), in which specific proteins are "stained" so that they can be seen under the microscope. Immunohistochemistry is widely used to diagnose cancer and can also help predict the likely outcome (prognosis) based on the tumor-specific antigen.

Monoclonal antibodies have also been applied to home pregnancy tests which work by binding to the antigen of a hormone called human chorionic gonadotropin (hCG).

The same principles are applied to home ovulation kits in which monoclonal antibodies bind to the antigen of luteinizing hormone (LH).

Therapeutic Uses of Monoclonal Antibodies

In recent years, monoclonal antibodies have increasingly been used to treat a wide range of medical conditions. In fact, since the introduction of Orthoclone OKT3 in 1986, there have been no less than 100 monoclonal antibodies licensed as drugs by the FDA.

In medicine, monoclonal antibodies are used as a form of immunotherapy in which you stimulate the immune system to fight disease. Because of the way that they work, monoclonal antibodies can also be considered a form of targeted therapy, in which specific cells are targeted and (unlike with chemotherapy) others are left untouched.

Cancer is one of the diseases in which monoclonal antibodies play an increasingly important role. But, there are other conditions, including autoimmune diseases, that benefit from monoclonal antibody therapy.

Drug Names

Monoclonal antibody drugs are often recognized by the suffix "mab"—the abbreviation for monoclonal antibody—at the end of their name. Examples include Avastin (bevacizumab) used to treat colon cancer and Entyvio (vedolizumab) used to treat inflammatory bowel disease (IBD).

Therapy Types

Monoclonal antibodies work in different ways to fight disease. Some bind to defensive white blood cells to make them more efficient, while others "tag" cells for destruction by medications or radiation.

The five types of therapies that deliver and use monoclonal antibodies in different ways are:

  • Antibody-directed enzyme prodrug therapy (ADEPT): This is used to deliver cytotoxic (cell-killing) drugs to specific cancer sites. It works by attaching a prodrug (an inactive form of a drug) to the antigen of a tumor, thereafter converting it into an active drug.
  • Antibody-drug conjugates (ADC): This works similarly to ADEPT, but instead of delivering a prodrug, it delivers an active cytotoxic drug directly to its target.
  • Checkpoint therapy: This is used to block proteins produced by tumors, called checkpoints, that "turn off" defensive white blood cells, called T cells, By blocking the attachment of checkpoints to T cells, the immune system is better able to fight cancer.
  • Immunoliposome therapy: This combines a monoclonal antibody with a fat-based shell called a liposome to deliver drugs used to treat cancer, infectious diseases, autoimmune disorders, and neurodegenerative diseases like Alzheimer's (a progressive neurological disorder), among others.
  • Radioimmunotherapy: This involves the use of radioactively changed monoclonal antibodies that bind to tumor cells and kill them. This includes blood cancers like lymphoma and multiple myeloma.

Treatment of Cancer

There are at least 25 monoclonal antibodies licensed for the treatment of different cancers, including:

Monoclonal antibody therapies are often reserved for advanced metastatic cancer. This is when cancer has spread beyond the original tumor, and the treatment is focused on slowing disease progression and prolonging life.

What to Expect

Monoclonal antibodies for cancer are delivered intravenously (IV, within a vein) in a cancer treatment center. The IV infusion usually takes only 20 to 25 minutes, but you would be asked to wait for an hour before leaving to ensure you don't have an allergic reaction.

Treatment of Autoimmune Diseases

Autoimmune diseases are those in which the immune system mistakenly attacks its own cells. There are at least 20 different monoclonal antibodies licensed for the treatment of autoimmune diseases such as:

Monoclonal antibodies used for these conditions work in different ways. Some bind to proteins that trigger damaging autoimmune inflammation. These include proteins known as tumor necrosis factor (TNF) and interleukin (IL), both of which are linked to many autoimmune conditions.

Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab) are three monoclonal antibodies classified as TNF inhibitors, while Actemra (tocilizumab) is one of the better-known IL inhibitors.

Other monoclonal antibodies like Rituxan (rituximab) target B cells that produce harmful antibodies, known as autoantibodies, that initiate the autoimmune assault.

What to Expect

Monoclonal antibodies used to treat autoimmune diseases may be given intravenously or by subcutaneous injection (under the skin) in a healthcare provider's office or infusion center. Because the drugs are typically given in smaller doses, it can take weeks or months to reap the full benefits of treatment.

Other Uses

Many monoclonal antibodies have multiple indications and can be used to treat different diseases. At the same time, there are newer monoclonal antibodies that specifically target and treat diseases unrelated to cancer or autoimmunity.

These include monoclonal antibodies licensed for the treatment of:

There are also monoclonal antibodies used for the prevention of kidney transplant rejection, migraine headaches, and recurrent Clostridium difficile infection.

Researchers are also investigating monoclonal antibodies (such as aducanumab and lecanemab) that may one day treat neurodegenerative disorders like Alzheimer's disease or Parkinson's disease.

Side Effects

As valuable as monoclonal antibodies are for the treatment of cancer and other diseases, they can cause sometimes significant side effects. The side effects can vary from one drug to the next and tend to be more profound when delivered intravenously (due in large part to the size of the dose).

The risk of side effects tends to be dose-dependent, meaning higher doses translate to a higher risk (or severity) of side effects.

With that said, monoclonal antibodies used to treat autoimmune diseases are often used on an ongoing basis to maintaining control of symptoms. The extended use of these drugs can have a cumulative effect, suppressing the immune function and causing side effects even at lower doses.

When use for the treatment of cancer, common side effects of monoclonal antibodies may include:

  • Injection site reactions
  • Fever
  • Chills
  • Weakness
  • Headache
  • Diarrhea
  • Nausea or vomiting
  • Dizziness or light-headedness
  • Fainting
  • Rashes

When used for the treatment of autoimmune diseases and other chronic illnesses, common side effects may include:

Possible Complications

The prolonged use of monoclonal antibodies is associated with an increased risk for all types of infections, including tuberculosis (TB) and potentially severe fungal infections like invasive candidiasis (in which a yeast infection spreads to internal organs).

Monoclonal antibodies can also cause the reactivation of TB and hepatitis B. People prescribed monoclonal antibodies should be tested for TB and hepatitis B before starting treatment in the event the diseases are undiagnosed.

Monoclonal antibodies can also trigger a potentially life-threatening reaction known as anaphylaxis, which, if left untreated, can lead to shock, coma, asphyxiation, organ failure, and death.

Anaphylaxis doesn't usually occur with the first monoclonal treatment but only after a person has been reexposed to the drug. Symptoms tend to develop one to two hours after treatment.

When to Seek Emergency Care

Call 911 or have someone rush you to the nearest emergency room if you experience the following signs of anaphylaxis after receiving monoclonal antibodies:

  • Shortness of breath
  • Wheezing
  • A sudden outbreak of rash or hives
  • Slowed or irregular heartbeats
  • Nausea and vomiting
  • Sudden diarrhea
  • Swelling of the face, tongue, or throat
  • A feeling of impending doom

Summary

Monoclonal antibodies are artificially produced antibodies that can be used to diagnose, treat, or prevent an ever-widening array of diseases and medical conditions, including cancer, autoimmune diseases, and COVID-19.

There are more than 100 monoclonal antibodies licensed as drugs by the FDA. Some are given by intravenous (IV) infusion, while others are delivered by subcutaneous injection.

Traditionally, the production of monoclonal antibodies involved mice, but modern production techniques will either fuse, graft, or insert the genetic material of mouse antibodies onto human antibodies to prevent the immune system from attacking them. They can also be made entirely in the test tube with recombinant DNA technology.

Despite their numerous benefits, monoclonal antibodies can cause side effects, particularly when given in high doses or over extended periods of time.

A Word From Verywell

As scientists learn more about the mechanism of diseases—and the role that specific antibodies play in them—there are expected to be many more monoclonal antibodies licensed for use by the FDA. There are hundreds of experimental or investigation antibodies in various stages of testing or development, dozens of which are solely intended to treat or prevent COVID-19.

If prescribed monoclonal antibodies for any reason, be sure to ask as many questions as you need to understand the benefits and risks. While monoclonal antibodies are definite game-changers for many diseases, they have their limitations and may not be the "magic bullet" you presume them to be.

By speaking with your healthcare provider, you can be fully prepared for treatment and better able to avoid possible side effects and complications.

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Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By James Myhre & Dennis Sifris, MD
Dennis Sifris, MD, is an HIV specialist and Medical Director of LifeSense Disease Management. James Myhre is an American journalist and HIV educator.