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
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.
Interleukin-2 (IL-2) helps immune system cells grow and divide more quickly. A man-made version of IL-2 is approved to treat advanced kidney cancer and metastatic melanoma.
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. 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 are chemicals that help the body resist virus infections and cancers. The types of interferon (IFN) are named after the first 3 letters of the Greek alphabet:
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.
IFN-alfa can be used to treat 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
- 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.
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.
Immune checkpoint inhibitors
These drugs target molecules like PD-1, PD-L1, and CTLA-4, which normally help keep the immune system in check. While these checkpoint proteins are important in stopping the immune system from attacking normal cells, they can also stop it from attacking cancer cells. These drugs help boost the immune response against some cancers.
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.
These drugs can also cause severe birth defects if taken during pregnancy.
Bacille Calmette-Guérin (BCG) is a germ that doesn’t 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 used to treat early stage bladder cancer. It is a liquid put into the bladder through a catheter. BCG attracts the body’s immune system cells to the bladder, where they can attack 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 is applied to the skin as a cream. It 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 in 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.