Immunotherapy refers to types of treatment that stimulate, enhance or suppress the body's own immune system. Immunotherapy is used to treat certain types of cancer and inflammatory diseases, such as rheumatoid arthritis, Crohn's disease and multiple sclerosis. It also is called biological therapy, biotherapy or biological response modifier (BRM) therapy.

The body's immune system recognizes and attacks bacteria and other foreign material. Our natural defenses also can recognize cancer cells as foreign or abnormal. Unlike normal cells, cancer cells have unique proteins called antigens on the outer cell surface. Antibodies are proteins produced by the immune system. They latch onto the cancer cells' antigens and label or tag the abnormal cells. If the immune system always worked perfectly, chemical signals would recruit special cells in the immune system to destroy the tagged cancer cells. However, the immune system does not always work perfectly on its own.

Immunotherapy helps to stimulate the immune system to fight cancer. The chemicals used in immunotherapy often are called biological response modifiers because they enhance the body's normal immune-system reaction to a cancer threat. Some biological response modifiers are chemicals that occur naturally in the body but have been produced in larger amounts in a laboratory to help boost a person's immune response. Biological response modifiers can play many different roles in fighting cancer. They can recruit more immune system cells to attack a tumor. Or they can make cancer cells more vulnerable to an attack by the immune system. Some biological response modifiers also can change the way cancer cells grow, coaxing them into behaving more like normal cells.

Immunotherapy also can be used to suppress the immune system. This is particularly helpful in autoimmune disorders in which the immune system "misfires" and inappropriately attacks normal tissues. Inflammation, which serves a useful purpose when fighting infection, only serves to damage normal tissues in autoimmune disease. Biological therapies can cool off this harmful inflammation.

Here are some examples of immunotherapy currently in use:

• Interferons � These chemicals boost the body's immune response. They also can act directly on cancer cells to control their rapid growth.



• Interleukins � These chemicals can stimulate growth of the body's immune cells, especially lymphocytes (a type of white blood cell).



• Colony stimulating factors � These chemicals encourage the growth of bone marrow stem cells. Bone-marrow stem cells, especially white blood cells, are needed to fight infections. But they often are destroyed by chemotherapy or radiation therapy given to treat cancer. Colony stimulating factors (for example GCSF or GMCSF) are used after other cancer therapies to help grow a new population of cells in the blood.



• Monoclonal antibodies � These antibodies, made in a laboratory, recognize the antigens on the surface of cancer cells. They can be used alone or linked to anti-cancer drugs or to radioactive substances. They can carry these linked poisons directly to tumor cells inside the body. Some antibodies acting alone can interfere with the cancer cells enough to stop them from growing or to cause them to be destroyed by the body's immune system. Monoclonal antibodies spare the body's normal cells, because these cells don't carry the cancer cells' telltale foreign antigens, or at least not as many. Monoclonal antibodies may help people with autoimmune diseases by targeting certain immune cells or chemical messengers (called cytokines) involved in inflammation. For example, monoclonal antibodies may reduce pain and improve joint function in people with rheumatoid arthritis.

Tumor vaccines show a lot of promise. Just as vaccines have been used to teach the body how to fight infections, tumor vaccines can boost the body's immune-system attack against cancer. They also may be able to prevent tumors from coming back after cancer therapy is finished.

Different forms of biological response modifiers currently are being used against many different types of cancer. One type of interferon, called interferon alpha-2a, has been used to treat kidney cancer, Kaposi's sarcoma, melanoma and certain types of leukemia and lymphoma. Interleukin-2 (IL-2) may be effecitve for kidney cancer and advanced melanoma.

Rituximab (Rituxan) was the first monoclonal antibody approved by the FDA for use against a type of lymphoma. Rituximab is also approved to treat rheumatoid arthritis that is not responding to other agents. Other FDA-approved monoclonal antibody treatments include abatacept (Orencia) for rheumatoid arthritis and trastuzumab (Herceptin) for breast cancer. Tumor vaccines are still being tested in clinical trials but have been used for malignant melanoma, breast cancer, kidney cancer, colorectal cancer, pancreatic cancer, prostate cancer and other cancers.

Immunotherapy that inhibits the production of tumor necrosis factor (anti-TNF therapy) is one of the most effective strategies for treating rheumatoid arthritis and other inflammatory diseases when conventional drugs are insufficient. Anti-TNF medications include adalimumab (Humira), infliximab (Remicade) and etanercept (Enbrel).

If you are going to be treated with interferon alpha-2a, your doctor will ask if you have a history of heart disease or allergies to certain medicines. Before you begin therapy, your doctor will order blood tests to check your liver function and your level of various blood cells. Your doctor also will ask you about any history of depression or other psychiatric problems. This is because interferon alpha-2a has been associated with an increased risk of depression and possibly suicide.

People receiving abatacept, adalimumab, etanercept, infliximab or rituximab should be screened for exposure to tuberculosis with a skin test and chest X-ray. Your doctor also will ask whether you have had any prior infections, heart disease, lung disease, cancer or diseases of the nervous system.

Some forms of immunotherapy are still experimental. How you're prepared for them will vary according to the specific experimental protocol, or written plan, for testing the drug.

Interferon alpha-2a, adalimumab and etanercept are given by injection. Your doctor or an assistant will show you how to prepare the needle and syringe and how to inject yourself. If you feel too weak or ill to give yourself the injection, your doctor will arrange for a family member or other caregiver to learn the injection technique and give you your medication.

Usually, the IL-2 and monoclonal antibodies are given intravenously (into a vein), just as chemotherapy is given. If you agree to participate in an experimental study for other types of immunotherapy, you will learn about the specific treatment steps, as well as the benefits and risks, beforehand.

Your doctor may use many different tests to monitor the effects of your immunotherapy. These include physical examinations, blood tests, X-rays and scans.

Risks and side effects associated with different types of immunotherapy include the following:

• Swelling
• Redness or infection at the injection site
• Rashes
• Allergic reactions
• Flulike symptoms, such as fever, muscle aches, chills and fatigue
• Digestive problems
• Changes in blood pressure or myocarditis (heart inflammation)
• Kidney failure
• Low levels of white blood cells (infection-fighting cells)
• Thinning hair
• Infection, including tuberculosis, especially in people with prior exposure

Interferon alpha-2a also may be linked to depression and suicidal behavior. Herceptin generally has few side effects. However, in a small but significant number of cases, it has been associated with congestive heart failure and cardiomyopathy. These cases have usually been treatable and reversible.

Call your doctor immediately if you develop any of the following side effects:

• Pain
• Redness or swelling at the injection site
• A rash or hives
• Light-headedness
• Difficulty breathing
• A tight feeling in your throat
• Fever, cough or flulike symptoms
• Any other problems that your doctor may warn you about

Also, call your doctor at the first sign of depression, even if you think it might just be a passing case of the blues.

Clinicaltrials.gov
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American Cancer Society (ACS)
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http://www.cancer.org/