Non-specific cancer immunotherapies and adjuvants
Non-specific immunotherapies don’t target cancer cells specifically. They stimulate the immune system in a more general way, but this can still sometimes lead to a better immune response against cancer cells.
Some non-specific immunotherapies are 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 are chemicals made by some immune system cells. They are crucial in controlling the growth and activity of other immune system cells and blood cells in the body.
Cytokines are injected, either under the skin, into a muscle, or into a vein. The most common ones are discussed here.
Interleukins are a group of cytokines that act as chemical signals between white blood cells.
IL-2 can be used as a single drug treatment for these cancers, or it can be combined with chemotherapy or with other cytokines such as interferon-alfa. (It is also being studied for use as an adjuvant 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 can 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 possible side effects, if IL-2 is given in high doses, it must be done in a hospital.
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, 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 (CML)
- Follicular non-Hodgkin lymphoma
- Cutaneous (skin) T-cell lymphoma
- Kidney cancer
- Kaposi sarcoma
Side effects of interferons can 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 for many people to tolerate. Most side effects don’t 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 (GM-CSF)
This cytokine causes the bone marrow to make more of certain types of immune system cells and blood cells. A man-made version, known as sargramostim (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.
Drugs that target immune system checkpoints
A very important part of the immune system is its ability to keep itself from attacking other normal cells in the body. To do this, it uses “checkpoints” – molecules on immune cells that need to be activated (or inactivated) to start an immune response. Cancer cells sometimes find ways to use these checkpoints to avoid being attacked by the immune system. But newer drugs that target these checkpoints hold a lot of promise as cancer treatments.
Drugs that target CTLA-4
CTLA-4 is a protein found on the surface of immune cells called T cells in the body. It normally acts as a type of “off switch” that helps keep the T cells in check, preventing them from attacking other cells in the body. Unfortunately this can also stop them from attacking cancer cells.
Ipilimumab (Yervoy®) is a monoclonal antibody that attaches to CTLA-4 and stops it from working. This boosts the immune response against cancer cells in the body.
This drug is used to treat melanomas that can’t be removed by surgery or that have spread to other parts of the body. It doesn’t seem to cure the melanoma, but it has been shown to help some people live longer. Ipilimumab is also being studied for use against other cancers.
One concern with this drug is that it can allow the immune system to attack some normal organs in the body, which can lead to serious side effects in some people. The most common side effects include fatigue, diarrhea, skin rash, and itching. Less often it can cause more serious problems in the intestines, liver, hormone-making glands, nerves, skin, eyes, or other organs. In some people these side effects have been fatal.
Drugs that target PD-1 or PDL-1
PD-1 is another protein on the surface of some T cells. Compared to CTLA-4, it seems to be found more often in T cells in inflamed tissues and tumors, where it helps keep the immune response under control. It does this when it attaches to PD-L1, a protein found on some normal (and cancer) cells. When PD-1 binds to PD-L1, it basically tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1 on their surfaces, which helps them evade immune attack.
Drugs that target either PD-1 or PD-L1 can boost the immune response against cancer and have shown a great deal of promise in clinical trials. They may have fewer side effects than ipilimumab. Pembrolizumab (Keytruda) is a monoclonal antibody that blocks PD-1 that has recently been approved to treat advanced melanoma. For more information, see the section “What’s new in cancer immunotherapy research?”
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, lenalidomide, and pomalidomide
Thalidomide (Thalomid®), lenalidomide (Revlimid®), and pomalidomide (Pomalyst®) are known as immunomodulating drugs (or IMiDs). They are thought to work in a general way by boosting the immune system, although it’s not exactly clear how they do this. These drugs are used to treat multiple myeloma and some other cancers.
The drugs can cause side effects such as drowsiness, fatigue, constipation, low blood cell counts, and neuropathy (painful nerve damage). There is also an increased risk of serious blood clots (that start in the leg and can travel to the lungs). These tend to be more likely with thalidomide than with the other drugs.
Because of concerns these drugs can cause severe birth defects if taken during pregnancy, they can only be obtained through special programs run by the drug company that makes them.
Bacille Calmette-Guérin (BCG) is a germ that 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 a liquid put 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 can 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 can also be used to treat some melanoma skin cancers by injecting it directly into the tumors.
Imiquimod (Zyclara®) 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 have serious skin reactions to this drug.
Last Medical Review: 03/19/2014
Last Revised: 09/05/2014