Monoclonal antibody drugs for cancer treatment: How they work

If you're considering monoclonal antibody therapy as part of your cancer treatment, learn about these drugs and carefully weigh the benefits against the potential side effects.

Monoclonal antibody drugs are a relatively new innovation in cancer treatment. The Food and Drug Administration (FDA) approved the first monoclonal antibody for cancer treatment in 1997. Today several of these drugs are available for treating certain cancers.

But because monoclonal antibody treatment is so new, the best way to use this new therapy isn't always clear. If you and your doctor are considering using a monoclonal antibody as part of your cancer treatment, find out what to expect from this therapy. Together you and your doctor can decide whether a monoclonal antibody treatment may be right for you.

What is a monoclonal antibody?

A monoclonal antibody is a laboratory-produced molecule that can be targeted to attach to specific substances on cancer cells. Your body naturally produces antibodies as part of your immune system's response to germs and other invaders. The laboratory-produced monoclonal antibodies used in cancer treatment are carefully engineered to target specific defects in your cancer cells.

How do monoclonal antibody drugs work?

When a monoclonal antibody attaches to a cancer cell, it can:

• Make the cancer cell more visible to the immune system. The immune system attacks foreign invaders in your body, but it doesn't always recognize cancer cells as enemies. A monoclonal antibody can be directed to attach to certain parts of a cancer cell, thus marking the cancer cell and making it easier for the immune system to find.

  The monoclonal antibody drug rituximab (Rituxan) attaches to a specific protein (CD20) only found on B cells, one type of white blood cell. Certain types of lymphomas arise from these same B cells. When rituximab attaches to the protein on the B cells, it makes the cells more visible to the immune system, which can then attack. Rituximab lowers the number of B cells, including your healthy B cells, but your body produces new healthy B cells to replace these. The cancerous B cells are less likely to recur.

• Block growth signals. Chemicals called growth factors attach to receptors on the surface of normal cells and cancer cells, signaling the cells to grow. Certain cancer cells make extra copies of the growth factor receptor, thus making them grow faster than the normal cells. Monoclonal antibodies can block these receptors and prevent the growth signal from getting through.

  Cetuximab (Erbitux), a monoclonal antibody approved to treat colon cancer and head and neck cancer, attaches to receptors on cancer cells that accept a certain growth signal (epidermal growth factor). Cancer cells and some healthy cells rely on this signal to tell them to divide and multiply. Doctors hope blocking the signal from reaching its target on the cancer cells may slow or stop the cancer from growing.

• Deliver radiation to cancer cells. By combining a radioactive particle with a monoclonal antibody, doctors can deliver radiation directly to the cancer cells. This way, most of the surrounding healthy cells aren't harmed. Radiation-linked monoclonal antibodies deliver a low level of radiation over a longer period of time, which researchers believe is as effective as the more conventional high-dose external beam radiation.

  Ibritumomab (Zevalin), approved for non-Hodgkin's lymphoma, combines a monoclonal antibody with two radioactive particles. The ibritumomab monoclonal antibody attaches to receptors on cancerous blood cells and delivers the radiation.

• Slip powerful drugs into cancer cells. Powerful anti-cancer drugs or toxins can be attached to monoclonal antibodies. The drugs remain inactive until they're inside the target cells, lowering the chance of harming other cells.

  Gemtuzumab (Mylotarg), approved for treating a certain type of acute myelogenous leukemia, is a monoclonal antibody attached to a potent anti-cancer drug made from a bacterium. The monoclonal antibody in gemtuzumab attaches to specific receptors on leukemic cells. Then the anti-cancer drug enters the cancer cell and is activated, causing the cancer cell to die.

A number of monoclonal antibody drugs are available to treat various types of cancer. Clinical trials are studying monoclonal antibody drugs in treating nearly every type of cancer.

How are monoclonal antibody drugs used in cancer treatment?

Monoclonal antibody drugs were initially used to treat advanced cancers that hadn't responded to chemotherapy or cancers that had returned despite treatment. However, because these treatments have proved to be effective, certain monoclonal antibody treatments are being used earlier in the course of the disease. For instance, rituximab can be used as an initial treatment in some types of non-Hodgkin's lymphoma, and trastuzumab (Herceptin) is used in the treatment of some forms of early breast cancer.

Many of the monoclonal antibody therapies are still considered experimental. For this reason, these treatments are usually reserved for advanced cancers that aren't responding to standard, proven treatments.

Source: Food and Drug Administration, Center for Drug Evaluation and Research

Monoclonal antibodies are administered through a vein (intravenously). How often you undergo monoclonal antibody treatment depends on your cancer and what drug you're receiving. Some monoclonal antibody drugs may be used in combination with other treatments, such as chemotherapy. Others are administered alone.

What types of side effects do monoclonal antibody drugs cause?

Monoclonal antibody treatment for cancer may cause side effects, some of which, though rare, can be very serious. Talk to your doctor about what side effects are associated with the particular drug you're receiving.

In general, the more common side effects caused by monoclonal antibody drugs include:

• Allergic reactions, such as hives or itching
• Flu-like symptoms, including chills, fatigue, fever and muscle aches and pains
• Low blood cell counts, which may lead to bleeding, fatigue and infection
• Nausea
• Diarrhea
• Skin rashes

Rare, but more serious side effects of monoclonal antibody therapy may include:

• Infusion reactions. Severe allergy-like reactions can occur and, in a very small number of instances, lead to death. You may receive medicine to block an allergic reaction before you begin monoclonal antibody treatment. Infusion reactions usually occur while treatment is being administered or soon after, so your health care team will watch you closely for a reaction.
• Dangerously low blood cell counts. Low levels of red blood cells, white blood cells and platelets may lead to serious complications.
• Heart problems. Certain monoclonal antibodies may cause heart problems, including heart failure and a small risk of heart attack.
• Skin problems. Sores and rashes on your skin can lead to serious infections in some cases. Serious sores can also occur on the skin that lines your cheeks and gums (mucosa).
• Bleeding. Some of the monoclonal antibody drugs are designed to stop cancer from forming new blood vessels. There have been reports that these medications can cause bleeding.

How are monoclonal antibody drugs being studied?

Cancer researchers are continuing to study already-approved monoclonal antibody drugs to determine how best to use them to treat cancer. Clinical trials comparing monoclonal antibodies with other standard treatments may help doctors decide if monoclonal antibody therapy should be used sooner, rather than after other treatments have failed. These studies can also determine whether monoclonal antibodies might work best when combined with other treatments.

Cancer researchers are also working to develop new monoclonal antibodies. As they come to better understand the particular cellular changes associated with each type of cancer, researchers are discovering new targets for monoclonal antibodies.

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