Non-specific immunotherapies and adjuvants

Non-specific immunotherapies do not target a certain cell or antigen. They stimulate the immune system in a very general way, but this may still result in more activity against cancer cells.

Some non-specific immunotherapies can be given by themselves as cancer treatments. Others are used as adjuvants (along with a main treatment) to boost the immune system to improve how well another type of immunotherapy (such as a vaccine) works. Some are used by themselves against some cancers and as adjuvants against others.

Cytokines

Cytokines (pronounced SY-toh-kines) are chemicals made by immune system cells. They are crucial in controlling the growth and activity of other immune system cells and blood cells in the body.

Man-made versions of some cytokines can be given alone to boost the immune system, or they can be given along with tumor vaccines as adjuvants.

Some man-made cytokines are used to lessen the side effects of other treatments such as chemotherapy. They can help the bone marrow make more white blood cells, red blood cells, or platelets when their levels in the body have gotten too low. While this is important in cancer treatment, it isn't truly immunotherapy.

Cytokines are injected, either under the skin, into a muscle, or into a vein. The most common ones are discussed here.

Interleukins

Interleukins are a group of cytokines that act as chemical signals between white blood cells.

Interleukin-2 (IL-2) helps immune system cells grow and divide more quickly. When a man-made version of IL-2 was approved by the US Food and Drug Administration in 1992 to treat advanced kidney cancer, it became the first true immunotherapy approved to be used alone in treating cancer. Since that time, it has also been approved to treat people with metastatic melanoma.

IL-2 can be used as a single drug treatment for these cancers, or it may be combined with chemotherapy or with other cytokines such as interferon-alfa. (It is also being studied for use as an adjuvant along with some vaccines.) Using IL-2 with these treatments might help make them more effective against some cancers, but the side effects of the combined treatment are also increased.

Side effects of IL-2 may include flu-like symptoms such as chills, fever, fatigue, and confusion. Most people gain weight. Some have nausea, vomiting, or diarrhea. Many people develop low blood pressure, which can be treated with other medicines. Rare but potentially serious side effects include an abnormal heartbeat, chest pain, and other heart problems. Because of these potential side effects, if IL-2 is given in high doses, it must be done in the hospital (as an inpatient).

Other interleukins, such as IL-7, IL-12, and IL-21, are now being studied for use against cancer too, both as adjuvants and as stand-alone agents.

Interferons

These cytokines, first discovered in the late 1950s, help the body resist virus infections and cancers. The types of interferon (IFN) are named after the first 3 letters of the Greek alphabet: IFN-alfa, IFN-beta, and IFN-gamma.

Only IFN-alfa is used to treat cancer. It boosts the ability of certain immune cells to attack cancer cells. It may also slow the growth of cancer cells directly, as well as the blood vessels that tumors need to grow.

The FDA has approved IFN-alfa for use against these cancers:

• Hairy cell leukemia
• Chronic myelogenous leukemia
• Follicular non-Hodgkin lymphoma
• Cutaneous (skin) T-cell lymphoma
• Kidney cancer
• Melanoma
• Kaposi sarcoma

Side effects of interferons may include flu-like symptoms (chills, fever, headache, fatigue, loss of appetite, nausea, vomiting), low white blood cell counts (which increase the risk of infection), skin rashes, and thinning hair. These side effects can be severe and can make treatment with interferon hard to tolerate for many people. Most side effects do not last long after the treatment stops, but fatigue can last longer. Other rare long-term effects include damage to nerves, including those in the brain and spinal cord.

Granulocyte-macrophage colony-stimulating factor

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that causes the bone marrow to make more of certain types of immune system cells and blood cells. A man-made version (known as sargramostim or Leukine^®) is often used to boost white blood cell counts after chemotherapy.

GM-CSF is also being tested against cancer as a non-specific immunotherapy and as an adjuvant given with other types of immunotherapies. Clinical trials of GM-CSF, alone or with other immunotherapies, are being done in people with many different types of cancer.

Common side effects of GM-CSF include flu-like symptoms (fever, headaches, muscle aches), rashes, facial flushing, and bone pain.

Other drugs that boost the immune system

Some other drugs boost the immune system in a non-specific way, similar to cytokines. But unlike cytokines, these drugs are not naturally found in the body.

Thalidomide

Thalidomide (Thalomid^®) is used as a treatment for multiple myeloma and some other cancers. It is thought to work in a general way by boosting the immune system, although it’s not exactly clear how it does this.

Side effects of thalidomide can include drowsiness, fatigue, severe constipation, and neuropathy (painful nerve damage). The neuropathy can be severe, and may not go away after the drug is stopped. There is also an increased risk of serious blood clots (that start in the leg and can travel to the lungs). Because thalidomide causes severe birth defects if taken during pregnancy, this drug can only be obtained through a special program run by the drug company that makes it.

Lenalidomide

Lenalidomide (Revlimid^®) is a newer drug that is similar to thalidomide. It is used to treat multiple myeloma and some other cancers.

The most common side effects of lenalidomide are low platelet and low white blood cell counts. It can also cause painful nerve damage. The risk of blood clots is not as great as that seen with thalidomide, but it is still increased. Like thalidomide, access to lenalidomide is tightly controlled out of concern about possible serious birth defects.

Bacille Calmette-Guérin

Bacille Calmette-Guérin (BCG) is a germ related to the one that causes tuberculosis. Unlike its bacterial "cousin," BCG does not cause serious disease in humans, but it does infect human tissues and helps activate the immune system. This makes BCG useful as a form of cancer immunotherapy. BCG was one of the earliest immunotherapies used against cancer and is still being used today.

BCG is FDA-approved for early stage bladder cancer. It is placed directly into the bladder through a catheter. The body's immune system cells are attracted to the bladder and activated by BCG, which in turn affects the bladder cancer cells. Treatment with BCG may cause symptoms that are like having the flu, such as fever, chills, and fatigue. It can also cause a burning feeling in the bladder.

BCG may also be used to treat some melanoma skin cancers by injecting it directly into the tumors.

Imiquimod

Imiquimod (Aldara^®) is a drug that, when applied as a cream, stimulates a local immune response against skin cancer cells. It is used to treat some very early stage skin cancers (or pre-cancers), especially if they are on sensitive areas such as on the face.

The cream is applied anywhere from once a day to twice a week for several months. Some people may have serious skin reactions to this drug.