A monoclonal antibody is a type of protein that is made in the laboratory and can bind to certain targets in the body, such as antigens on the surface of cancer cells. There are many kinds of monoclonal antibodies, and each monoclonal antibody is made so that it binds to only one antigen. Monoclonal antibodies are being used in the diagnosis and treatment of many diseases, including some types of cancer. They can be used alone or to carry drugs, toxins, or radioactive substances directly to cancer cells.

In addition to being crucial for our normal immune response, antibodies provide powerful tools for research and diagnostic purposes. The high specificity of antibodies makes them an excellent tool for detecting and quantifying a broad array of targets, from drugs to serum proteins to microorganisms. With in vitro assays , antibodies can be used to precipitate soluble antigens, agglutinate (clump) cells, opsonize and kill bacteria with the assistance of complement, and neutralize drugs, toxins, and viruses.

An antibody’s specificity results from the antigen-binding site formed within the variable regions —regions of the antibody that have unique patterns of amino acids that can only bind to target antigens with a molecular sequence that provides complementary charges and noncovalent bonds. There are limitations to antibody specificity, however. Some antigens are so chemically similar that cross-reactivity occurs; in other words, antibodies raised against one antigen bind to a chemically similar but different antigen. Consider an antigen that consists of a single protein with multiple epitopes (Figure 20.2). This single protein may stimulate the production of many different antibodies, some of which may bind to chemically identical epitopes on other proteins.

Cross-reactivity is more likely to occur between antibodies and antigens that have low affinity or avidity . Affinity, which can be determined experimentally, is a measure of the binding strength between an antibody's binding site and an epitope, whereas avidity is the total strength of all the interactions in an antibody-antigen complex (which may have more than one bonding site). Avidity is influenced by affinity as well as the structural arrangements of the epitope and the variable regions of the antibody. If an antibody has a high affinity/avidity for a specific antigen, it is less likely to cross-react with an antigen for which it has a lower affinity/avidity.

Some types of assays require better antibody specificity and affinity than can be obtained using a polyclonal antiserum. To attain this high specificity, all of the antibodies must bind with high affinity to a single epitope. This high specificity can be provided by monoclonal antibodies (mAbs). Table compares some of the important characteristics of monoclonal and polyclonal antibodies.

Unlike polyclonal antibodies, which are produced in live animals, monoclonal antibodies are produced in vitro using tissue-culture techniques. mAbs are produced by immunizing an animal, often a mouse, multiple times with a specific antigen. B cells from the spleen of the immunized animal are then removed. Since normal B cells are unable to proliferate forever, they are fused with immortal, cancerous B cells called myeloma cells, to yield hybridoma cells. All of the cells are then placed in a selective medium that allows only the hybridomas to grow; unfused myeloma cells cannot grow, and any unfused B cells die off. The hybridomas, which are capable of growing continuously in culture while producing antibodies, are then screened for the desired mAb. Those producing the desired mAb are grown in tissue culture; the culture medium is harvested periodically and mAbs are purified from the medium. This is a very expensive and time-consuming process. It may take weeks of culturing and many liters of media to provide enough mAbs for an experiment or to treat a single patient. mAbs are expensive (Figure).

Monoclonal antibodies (mAbs) are produced by introducing an antigen to a mouse and then fusing polyclonal B cells from the mouse's spleen to myeloma cells. The resulting hybridoma cells are cultured and continue to produce antibodies to the antigen. Hybridomas producing the desired mAb are then grown in large numbers on a selective medium that is periodically harvested to obtain the desired mAbs.

Since the most common methods for producing monoclonal antibodies use mouse cells, it is necessary to create humanized monoclonal antibodies for human clinical use. Mouse antibodies cannot be injected repeatedly into humans, because the immune system will recognize them as being foreign and will respond to them with neutralizing antibodies. This problem can be minimized by genetically engineering the antibody in the mouse B cell. The variable regions of the mouse light and heavy chain genes are ligated to human constant regions, and the chimeric gene is then transferred into a host cell. This allows production of a mAb that is mostly "human" with only the antigen-binding site being of mouse origin.

Humanized mAbs have been successfully used to treat cancer with minimal side effects. For example, the humanized monoclonal antibody drug Herceptin has been helpful for the treatment of some types of breast cancer. There have also been a few preliminary trials of humanized mAb for the treatment of infectious diseases, but none of these treatments are currently in use. In some cases, mAbs have proven too specific to treat infectious diseases, because they recognize some serovars of a pathogen but not others. Using a cocktail of multiple mAbs that target different strains of the pathogen can address this problem. However, the great cost associated with mAb production is another challenge that has prevented mAbs from becoming practical for use in treating microbial infections.

One promising technology for inexpensive mAbs is the use of genetically engineered plants to produce antibodies (or plantibodies). This technology transforms plant cells into antibody factories rather than relying on tissue culture cells, which are expensive and technically demanding. In some cases, it may even be possible to deliver these antibodies by having patients eat the plants rather than by extracting and injecting the antibodies. For example, in 2013, a research group cloned antibody genes into plants that had the ability to neutralize an important toxin from bacteria that can cause severe gastrointestinal disease. Eating the plants could potentially deliver the antibodies directly to the toxin.

Monoclonal antibodies provide higher specificity than polyclonal antisera because they bind to a single epitope and usually have high affinity. Monoclonal antibodies are typically produced by culturing antibody-secreting hybridomas derived from mice. mAbs are currently used to treat cancer, but their exorbitant cost has prevented them from being used more widely to treat infectious diseases. Still, their potential for laboratory and clinical use is driving the development of new, cost-effective solutions such as plantibodies.

Many monoclonal antibodies have been approved to treat a wide variety of cancers.

Monoclonal antibodies are immune system proteins that are created in the lab. Antibodies are produced naturally by your body and help the immune system recognize germs that cause disease, such as bacteria and viruses, and mark them for destruction. Like your body’s own antibodies, monoclonal antibodies recognize specific targets.

Many monoclonal antibodies are used to treat cancer. They are a type of targeted cancer therapy, which means they are designed to interact with specific targets. Learn more about targeted therapy.

Some monoclonal antibodies are also immunotherapy because they help turn the immune system against cancer. For example, some monoclonal antibodies mark cancer cells so that the immune system will better recognize and destroy them. An example is rituximab, which binds to a protein called CD20 on B cells and some types of cancer cells, causing the immune system to kill them. B cells are a type of white blood cell.

Other monoclonal antibodies bring T cells close to cancer cells, helping the immune cells kill the cancer cells. An example is blinatumomab (Blincyto®), which binds to both CD19, a protein found on the surface of leukemia cells, and CD3, a protein on the surface of T cells. This process helps the T cells get close enough to the leukemia cells to respond to and kill them.

Monoclonal antibodies can cause side effects, which can differ from person to person. The ones you may have and how they make you feel will depend on many factors, such as how healthy you are before treatment, your type of cancer, how advanced it is, the type of monoclonal antibody you are receiving, and the dose.

Doctors and nurses cannot know for sure when or if side effects will occur or how serious they will be. So, it is important to know which signs to look for and what to do if you start to have problems.

Like most types of immunotherapy, monoclonal antibodies can cause skin reactions at the needle site and flu-like symptoms.

Needle site reactions include:

• pain
• swelling
• soreness
• redness
• itchiness
• rash

Learn more about skin changes caused by cancer treatment.

Flu-like symptoms include:

• chills
• fatigue
• fever
• muscle aches and pains
• nausea
• vomiting
• diarrhea

Learn more about flu-like symptoms caused by cancer treatment.

Monoclonal antibodies can also cause:

• mouth and skin sores that can lead to serious infections
• high blood pressure
• congestive heart failure
• heart attacks
• inflammatory lung disease

Monoclonal antibodies can cause mild to severe allergic reactions while you are receiving the drug. In rare cases, the reaction is severe enough to cause death.

Some monoclonal antibodies can also cause capillary leak syndrome. This syndrome causes fluid and proteins to leak out of tiny blood vessels and flow into surrounding tissues, resulting in dangerously low blood pressure. Capillary leak syndrome may lead to multiple organ failure and shock.

Cytokine release syndrome can sometimes occur with monoclonal antibodies, but it is often mild. Cytokines are immune substances that have many different functions in the body, and a sudden increase in their levels can cause:

• fever
• nausea
• headache
• rash
• rapid heartbeat
• low blood pressure
• trouble breathing