Immunotherapy

What Is It?

Immunotherapy is a relatively new type of treatment that uses the body's own immune defenses to attack cancer. It also is called biological therapy, biotherapy or biological response modifier (BRM) therapy. Some types of immunotherapy are also used to treat noncancerous conditions such as rheumatoid arthritis, Crohn's disease and multiple sclerosis.

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. Next, chemical signals recruit special cells in the immune system to destroy the tagged cancer cells. However, the immune system often is not able to battle cancer successfully alone.

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 is a rapidly evolving area of therapy, and much of the work being done is still experimental. Among the types of immunotherapy being explored are:

• 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 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.

What It's Used For

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. Radioactive monoclonal antibodies ibritumomab tiuxetan (Zevalin) and tositumomab (Bexxar) may be effective in treating certain types of lymphoma. Rituximab is also under investigation as a treatment for rheumatoid arthritis. The monoclonal antibody trastuzumab (Herceptin) is FDA-approved to fight breast cancer. It is being tested against other types of cancers. 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.

Monoclonal antibodies, including adalimumab (Humira) and infliximab (Remicade), and a closely related immunotherapy, etanercept (Enbrel), are among the most effective medications for the treatment of rheumatoid arthritis and other types of arthritis.

Preparation

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.

Before you can be treated with trastuzumab, your doctor will ask about any history of heart disease and evaluate you for signs of heart disease.

People receiving adalimumab, etanercept or infliximab 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, cancer or diseases of the nervous system.

Most other 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.

How It's Done

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.

Follow-Up

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

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 been treatable and reversible.

When To Call A Professional

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 flu-like 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.

Additional Info

Clinicaltrials.gov

National Library of Medicine (NLM)

8600 Rockville Pike

Building 38

Bethesda, MD 20894

Toll-Free: 1-888-346-3656

http://www.clinicaltrials.gov/

American Cancer Society (ACS)

1599 Clifton Road, NE

Atlanta, GA 30329-4251

Toll-Free: 1-800-227-2345

http://www.cancer.org/