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 as treatments. Others are used as adjuvants (along with a main treatment) to boost immune system function to improve how well another therapy (such as a vaccine) works. And some immunotherapies 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 have a crucial role in regulating the growth and activity of other immune system cells and blood cells.

At this time, cytokines are often used in cancer treatment to lessen the side effects of other treatments such as chemotherapy. Man-made versions of cytokines 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.

But man-made versions of cytokines are also being used to boost the immune system and as adjuvants, which can be given along with tumor vaccines.

Cytokines are given as injections, 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. When interleukin-2 (IL-2) was approved by the FDA in 1992 to treat advanced kidney cancer, it became the first true immunotherapy approved for use 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 other forms of immunotherapy, such as vaccines. IL-2 helps immune system cells grow and divide more quickly.

Using IL-2 with chemotherapy or with other cytokines (such as interferon-alfa) may make these treatments more effective against some cancers. 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. An abnormal heartbeat occurs in less than 10% of patients. Chest pain and serious heart problems are rare. Because of these side effects, high doses of IL-2 must be given to the patient 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

This family of cytokines, first discovered in the late 1950s, helps 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. Although all 3 types of interferon are FDA approved to treat health conditions, only IFN-alfa is used to treat cancer. Not all of its actions are well understood, but it may work by:

• directly slowing the growth of cancer cells
• slowing down angiogenesis, the growth of new blood vessels that tumors must have in order to grow
• causing cancer cells to produce more antigens, making them easier for the immune system to see and destroy
• boosting the cancer cell-killing ability of natural killer (NK) cells and of other immune system cells that attack cancer with help from antibodies

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

• hairy cell leukemia
• chronic myelogenous leukemia
• follicular non-Hodgkin lymphoma
• cutaneous (affecting the 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 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/growth factor that causes the bone marrow to make more of certain types of immune system cells and blood cells. This includes monocytes, macrophages, and dendritic cells. It also boosts the production of other blood cells. A man-made version (also 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.

Adjuvants other than cytokines

Many other compounds are known to boost the activity of the immune system and are now being studied as possible adjuvants, particularly for use with vaccine therapies. Some of the most commonly studied adjuvants are listed below, but many more are being developed.

Bacille Calmette-Guérin

Bacille Calmette-Guérin (BCG) is a bacterium that is related to the germ 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 it is still being used today. It is FDA-approved as a routine treatment for early stage bladder cancer.

Its usefulness in other cancers as an adjuvant is also being tested. Researchers are looking at injecting BCG to give an added boost to the immune system when using chemotherapy, radiation therapy, or other types of immunotherapy.

Keyhole limpet hemocyanin

Keyhole limpet hemocyanin (KLH) is an adjuvant used to boost the effectiveness of cancer vaccine therapies. It is extracted from a type of sea creature related to the snail.

Incomplete Freund's adjuvant

Incomplete Freund's adjuvant (IFA) is given together with some experimental therapies to help stimulate the immune system and to increase the immune response to cancer vaccines. IFA is a water-in-oil emulsion that stimulates the T-cell immune response to antigens.

QS-21

QS-21 is a fairly new immune stimulant made from a plant extract that increases the immune response to some cancer vaccines.

DETOX ™

DETOX is newer adjuvant. It is made from parts of the cell walls of bacteria and a kind of fat that also comes from bacteria. Since it was first made, other types have been created by using other methods, such as DETOX-B and DETOX-PC, one of which has been named Melacine®. It is used with various immunotherapies to boost the immune system.

Dinitrophenyl

Dinitrophenyl (DNP) is a small molecule that can attach to tumor antigens and boost immune response. It is used to modify tumor cells in certain cancer vaccines.

Go back to Immunotherapy.

Last Medical Review: 08/25/2009
Last Revised: 10/27/2009