What Is a Monoclonal Antibody?

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, rabbit, horse, or other animal 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.⁷

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.

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

· 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.

Treatment of Cancer

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

· Bladder cancer

· Breast cancer

· Cervical cancer

· Colorectal cancer

· Gastric (stomach) cancer

· Hodgkin lymphoma

· Leukemia

· Lung cancer

· Melanoma

· Merkel cell carcinoma

· Multiple myeloma

· Non-Hodgkin lymphoma

· Renal (kidney) cancer

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.

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:

· Ankylosing spondylitis

· Crohn’s disease (a form of IBD)

· Juvenile idiopathic arthritis

· Lupus

· Multiple sclerosis (MS)

· Plaque psoriasis

· Psoriatic arthritis

· Rheumatoid arthritis (RA)

· Ulcerative colitis (a form of IBD)

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.

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:

· Age-related macular degeneration (AMD)

· Anthrax poisoning

· Eczema (atopic dermatitis)

· Familial hypercholesterolemia

· Hemophilia

· HIV (multidrug resistant)

· Postmenopausal osteoporosis

· Respiratory syncytial virus (RSV)

· Severe asthma

There are also monoclonal antibodies used for the prevention of kidney transplant rejection, migraine headaches, and recurrent Clostridium difficile infection.²⁴

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

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.

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