Monoclonal antibodies are the most widely used form of cancer immunotherapy at this time.

Monoclonal antibody therapy uses antibodies that are made in the lab rather than by a person's own immune system. This type of treatment is considered a form of passive immunotherapy. These treatments do not require the person's immune system to start the fight against the cancer. Once the antibodies are given, they can then recruit other parts of the immune system to destroy the cancer cells.

The first monoclonal antibodies were made in the lab by fusing a myeloma (a type of bone marrow cancer) cell from a mouse with a mouse B cell that makes a certain antibody. The cell that results from this fusion is called a hybridoma.

Combining a B cell that can recognize one special antigen and a long-lived myeloma cell makes the resulting hybridoma cell a long-lasting, antibody-making factory. Because the antibodies made are all identical clones made from a single (mono) hybridoma cell, they are called monoclonal antibodies (sometimes abbreviated as MoAbs or MAbs).

The first MAbs were made entirely from mouse cells. One problem with this is that the human immune system will see these antibodies as foreign (because they're from a different species) and then will mount a response against them. In the short term, this can sometimes cause allergic-type reactions. In the long term, it means that the antibodies may only work the first time they are given; after that, the body's immune system is primed to destroy them before they can be helpful.

Over time, researchers have learned how to replace some parts of these mouse antibody proteins with human parts. Depending on how much of the MAb is human, these are called chimeric or humanized antibodies. Some MAbs are now fully human, which means they are likely to be even safer and may be more effective than older MAbs.

An even newer approach uses fragments of antibodies instead of whole ones. Smaller pieces may be better able to reach a tumor, which may make them more effective.

Over the past 10 years or so, the Food and Drug Administration (FDA) has approved several MAbs to treat certain cancers, as seen in the table below.

Clinical trials of monoclonal antibody therapy are also being done on almost every type of cancer. As researchers have found more antigens that are linked to cancer, they have been able to make monoclonal antibodies against more and more cancers.

Monoclonal antibodies used to treat cancer

*conjugated monoclonal antibodies

Two types of monoclonal antibodies are used in cancer treatments:

• Naked monoclonal antibodies are those without any drug or radioactive material attached to them.
• Conjugated monoclonal antibodies are those joined to a chemotherapy drug, radioactive particle, or a toxin (a substance that poisons cells).

Naked monoclonal antibodies

Naked MAbs are the most commonly used MAbs at this time. Although they all work by attaching themselves to specific antigens, they can be helpful in different ways.

Markers for destruction

Some naked MAbs attach to cancer cells to act as a marker for the body's immune system to destroy them. Antibodies now in use in this group include:

Rituximab (Rituxan): Rituximab is used to treat B-cell non-Hodgkin lymphoma and some other diseases. It is a monoclonal antibody against the CD20 antigen, found on B cells. It works, in part, by labeling cells so that the immune system can attack them.

Ofatumumab (Arzerra): Ofatumumab is another antibody against the CD20 antigen. It is used mainly to treat chronic lymphocytic leukemia when other treatments are no longer effective.

Alemtuzumab (Campath): Alemtuzumab is an antibody against the CD52 antigen, which is found on both B cells and T cells. It is used to treat some patients with B-cell chronic lymphocytic leukemia.

Activation blockers

Some naked MAbs don't really interact with a person's own immune system. Their effects come from their ability to attach to the specific antigens that are working parts of cancer cells or other cells that help cancer cells grow, and stop them from working. These MAbs are also referred to as targeted therapies. Examples of FDA-approved MAbs of this type include:

Trastuzumab (Herceptin): Trastuzumab is an antibody against the HER2/neu protein. A large amount of this protein is present on tumor cells in some cancers. When HER2/neu is activated, it helps these cells grow. Trastuzumab stops these proteins from becoming active. It is used to treat breast cancers that have large amounts of this protein.

Cetuximab (Erbitux): Cetuximab is an antibody against the EGFR protein, which is present in large amounts on some tumor cells and helps them grow and divide. Cetuximab blocks the activation of EGFR. It is used to treat some advanced colorectal cancers as well as some head and neck cancers.

Panitumumab (Vectibix): This MAb also targets the EGFR antigen. It is used to treat some cases of advanced colorectal cancer.

Bevacizumab (Avastin): Bevacizumab targets the VEGF protein, which is normally made by tumor cells to attract new blood vessels to feed their growth. Bevacizumab attaches to VEGF, which blocks it from signaling for new blood vessels to form. This MAb is used along with chemotherapy to treat some colorectal, lung, breast, and kidney cancers, as welll as glioblastomas (a type of brain tumor). It is being studied for use against other cancers.

Some of these antibodies have been used for many years. At first they were used mostly after other treatments had stopped working. But more studies have been done and continue to be done. Now, these antibodies are being used earlier in the course of cancer treatment.

Side effects

Monoclonal antibodies are given intravenously (injected into a vein). Compared with side effects of chemotherapy, the side effects of naked MAbs are usually fairly mild and are often more like an allergic reaction. If they do occur, it is most often while the drug is first being given.

Possible side effects can include:

• fever
• chills
• weakness
• headache
• nausea
• vomiting
• diarrhea
• low blood pressure
• rashes

Some MAbs also have effects that are specific to the antigens they target. For instance, like most chemotherapy drugs, some can affect the bone marrow. This can cause lower levels of blood cells, which can increase the risk of bleeding and infection in some people.

Conjugated monoclonal antibodies

Conjugated MAbs are monoclonal antibodies that are attached to drugs, toxins, or radioactive substances. The MAbs are used as homing devices to take these substances directly to the cancer cells. The MAb circulates in the body until it can find and hook onto the target antigen. It then delivers the toxic substance where it is needed most. This lessens the damage to normal cells in other parts of the body.

Conjugated antibodies may pack more of a punch than naked MAbs, but for this reason they often cause more side effects, too. The side effects depend on which type of substance they're attached to.

Conjugated MAbs are also sometimes referred to as tagged, labeled, or loaded antibodies. They can be divided into groups depending on what they are linked to.

• MAbs with radioactive particles attached are referred to as radiolabeled, and therapy with this type of antibody is known as radioimmunotherapy (RIT).

• MAbs with chemotherapy drugs attached are often referred to as chemolabeled.

• MAbs attached to toxins are called immunotoxins.

Radiolabeled antibodies

Two radiolabeled antibodies have been approved to treat cancer.

• Ibritumomab tiuxetan (Zevalin) delivers radioactivity directly to cancerous B lymphocytes. It is used to treat B-cell non-Hodgkin lymphoma that has not responded to standard treatment.

• Tositumomab (Bexxar) is used to treat certain types of non-Hodgkin lymphoma that no longer respond to rituximab (Rituxan) or chemotherapy.

Aside from being used to treat cancer, radiolabeled antibodies can also be used along with special cameras to help find areas of cancer metastasis (spread) in the body. While some radiolabeled antibodies such as ProstaScint (for prostate cancer) have been approved by the FDA, their role in helping to detect cancer has been very limited so far.

Chemolabeled antibodies

These are being studied and are available in the United States only through clinical trials at this time. None have been approved by the FDA as of mid-2009.

Immunotoxins

Immunotoxins are made by attaching MAbs to bacterial toxins such as diphtheria toxin (DT) or pseudomonal exotoxin (PE40), or to plant toxins such as ricin A or saporin.

Immunotoxins have shown some early promise in shrinking a few cancers, particularly lymphomas. But some major problems still need to be solved before this new form of cancer treatment can be used more widely.

The only immunotoxin approved for treating cancer is gemtuzumab ozogamicin (Mylotarg). It has a toxin called calicheamicin, attached to an antibody against the CD33 antigen, which is present on most leukemia cells. Gemtuzumab is used to treat some people with acute myelogenous leukemia.

Another immunotoxin, BL22, showed promising results in early studies against some forms of chronic leukemia, even in patients who no longer responded to chemotherapy. In early clinical trials, about 2 out of 3 patients had complete responses to the treatment (no evidence of cancer) that lasted up to 2 years. A newer, improved version of this immunotoxin, known as HA22 (CAT-8015), is now being studied.

Clinical trials of other immunotoxins are also being done in people with certain leukemias, lymphomas, brain tumors, and other cancers.

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Last Medical Review: 08/25/2009
Last Revised: 10/27/2009