SkinCancerNet Article
Immunotherapy: What It is and How It Can Help Fight Cancer

The human body’s immune system can protect itself from cancer by:

  • Eliminating cancer before it becomes established

  • Attacking cancer cells after they become established

  • In rare cases, completely eliminating an established cancer to bring about spontaneous cure

Knowledge of how the immune system works to destroy cancer is the basis for a form of cancer treatment called immunotherapy. Also known as “biotherapy,” “biological response modifier therapy,” and “biological therapy,” the purpose of immunotherapy is to repair, stimulate or enhance the body’s immune responses to fight established cancer.

Scientists have created several types of immunotherapy to treat various forms of cancer, including skin cancer. These therapies are classified as “active” when they stimulate the patient’s own immune system to fight the cancer and “passive” when substances that the body produces are synthetically created in a laboratory and do not rely on the patient’s immune system to work.

Like chemotherapy, immunotherapy used to treat skin cancer can be topical (applied to the skin) or systemic (taken by pill, injection, or infusion).

Topical Immunotherapy
In mid-2004, a topical medication called imiquimod was approved by the U.S. Food and Drug Administration (FDA) for patients who have superficial basal cell carcinoma (one of the four types of basal cell carcinoma) and a normal immune system.

Imiquimod comes in cream form and is approved for treating superficial basal cell carcinoma (sBCC) tumors with a maximum diameter of 2.0 centimeters. Use is limited to certain areas of the body. Patients typically apply the cream once a day for approximately 5 to 7 weeks. If imiquimod is an option, the dermatologist will determine how often imiquimod should be applied. As the medication works, local skin reactions, such as redness, swelling, erosion, scabbing, scaling, and crusting occur. These are a normal and expected part of treatment. In a recent research study, a few patients with sBCC experienced headache, upper respiratory tract infection, or back pain. Patients must be willing to apply the medication as instructed and return for follow-up visits. The dermatologist will need to examine the area to see if the tumor has been destroyed. This determination should not be made by the patient, patient’s family, or friends.

It is important to know that imiquimod does not work for every patient, and another form of therapy may be necessary. The ability of imiquimod to sustain long-term clearance is still not known, and ongoing studies are evaluating the long-term effectiveness of this medication.

Systemic Immunotherapy
In systemic form, immunotherapy may be used alone but most often is part of a treatment plan that includes another cancer therapy, such as surgery, radiation, or chemotherapy. Since immunotherapy helps the body fight disease and infection, systemic immunotherapy is used to treat skin cancers that are at risk of spreading, such as certain melanomas and squamous cell carcinomas. Systemic immunotherapy also can lessen the side effects from other cancer treatments, such as chemotherapy. While systemic immunotherapy holds much promise for the treatment of cancer, it is still in the experimental phases. The hope is that systemic immunotherapy will eventually provide effective treatment for metastatic melanoma.

Types of systemic immunotherapy used to treat skin cancer include:

Cytokine Therapy
″Cytokines” are proteins released by cells in the immune system that help boost immunity. Two cytokines have been approved by the FDA for the treatment of metastatic melanoma:

  • Interferon-alpha

  • Interleukin-2 (IL-2)

In clinical trials, these two cytokines have helped shrink tumors in about 10% to 20% of patients with stage III and stage IV melanoma. It is believed that cytokines hold enormous potential for cancer therapy, and many cytokines are being studied in clinical trials because of their ability to enhance the body’s immune response to cancer cells.

Interferon. Interferons are substances within the immune system that are produced in response to infection. They are classified as alpha, beta, or gamma forms — depending on the chemical structure, biologic activities, and other criteria. Interferon-alpha is FDA-approved for treating melanoma in stage IIB (primary tumor is 4 millimeters or more) and stage III (spread to the lymph nodes) when used along with another therapy, such as surgery. In these stages, interferon-alpha helps prevent recurrence and increases the likelihood that all cancer is eliminated.

How interferon-alpha is administered. Following one month of intravenous infusion, interferon-alpha is usually given as a shot 3 times a week and may be given for up to one year. Research shows that this dosage proves more effective than giving the medication once a week or intermittently.

Side effects from interferon-alpha. High doses must be given for interferon-alpha to be effective; however, it is quite toxic in high doses. The dropout rate is significant because many patients cannot tolerate the side effects, which include flu-like symptoms, such as fever, chills, aches, fatigue, and a general feeling of illness. Interferon-alpha2b can also have adverse effects on the heart and liver. Patients should be treated by a physician who is experienced with this treatment and knows how to minimize the side effects.

Interleukin: Interleukins activate the “killer” activities of specific white blood cells in the immune system and are classified by number as IL-1, IL-2, or IL-3, etc. IL-2, which is used to treat metastatic melanoma, helps the immune cells reproduce more quickly. It may be used as a single medication or in combination with other medication to treat advanced melanoma. About 10% to 20% of patients respond to IL-2. In a few cases, high doses of IL-2 have produced long-term remissions.

How IL-2 is administered. IL-2 may be injected into the skin or a vein over a 15-minute period. It also may be given by infusion over 24 hours.

Side effects from IL-2. Accumulation of fluid in the body that causes the person to swell and feel quite ill is a possible side effect. For this reason, IL-2 therapy should be administered in a medical center experienced in its use. Other side effects include flu-like symptoms, confusion, and weight gain. Some people develop low blood pressure, which can be treated. A small percentage of patients develop an irregular heartbeat, chest pain, or serious heart problems.

Monoclonal Antibody Therapy
This type of therapy is showing much promise in treating many types of cancer, including melanoma; however, its effectiveness in treating melanoma is still being investigated in clinical trials. Monoclonal antibody therapy is proving effective when the patient’s immune system is weak since the immune system need not play an active role in fighting the cancer. It also is proving effective when other forms of treatment no longer work.

Monoclonal antibody therapy is known as "passive" immunotherapy because the antibodies (protein on the surface of B cells that work to attack foreign cells) are produced in the laboratory and then infused into the patient’s body. The antibodies are called "monoclonal" because they are identical clones produced from a single (mono) cell. Side effects are milder than those experienced with chemotherapy.

Vaccine Therapy
After years of research, melanoma vaccines are now being studied in clinical trials. Similar to vaccines that protect against viruses, such as polio and measles, melanoma vaccines inject the patient with small amounts of the substance to be destroyed. To get the body to attack melanoma, protein from melanoma cells is injected into the patient’s body. The patient’s immune system recognizes the protein as foreign and signals the immune system to attack and destroy the proteins. Some immune system cells retain the ability to recognize those foreign proteins. If the melanoma returns, the patient’s immune system should be able to recognize these cells as foreign and destroy them — preventing recurrence.

While immunotherapy shows much promise for treating skin cancer, especially melanoma, it is not appropriate treatment for everyone. Your physician can determine if immunotherapy is a treatment option for you.

Geisse, J et al. “Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: Results from two phase III, randomized, vehicle-controlled studies.” Journal of the American Academy of Dermatology. 2004 May;50(5):722-33.

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