Immune checkpoint inhibitors to treat cancer
An important part of the immune system is its ability to tell between normal cells in the body and those it sees as “foreign.” This lets the immune system attack the foreign cells while leaving the normal cells alone. To do this, it uses “checkpoints” – molecules on certain 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 drugs that target these checkpoints hold a lot of promise as cancer treatments.
Drugs that target PD-1 or PD-L1
PD-1 is a checkpoint protein on immune cells called T cells. It normally acts as a type of “off switch” that helps keep the T cells from attacking other cells in the body. It does this when it attaches to PD-L1, a protein 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, which helps them evade immune attack.
Monoclonal antibodies that target either PD-1 or PD-L1 can block this binding and boost the immune response against cancer cells. These drugs have shown a great deal of promise in treating certain cancers.
PD-1 inhibitors: Examples of drugs that target PD-1 include:
- Pembrolizumab (Keytruda)
- Nivolumab (Opdivo)
These drugs have been shown to be helpful in treating several types of cancer, including melanoma of the skin, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, and Hodgkin lymphoma. They are also being studied for use against many other types of cancer.
PD-L1 inhibitors: Examples of drugs that target PD-L1 include:
- Atezolizumab (Tecentriq)
- Avelumab (Bavencio)
These drugs have also been shown to be helpful in treating different types of cancer, including bladder cancer, non-small cell lung cancer, and Merkel cell skin cancer (Merkel cell carcinoma). They are also being studied for use against other types of cancer.
One concern with all of these drugs is that they can allow the immune system to attack some normal organs in the body, which can lead to serious side effects in some people. Common side effects of these drugs can include fatigue, cough, nausea, loss of appetite, skin rash, and itching. Less often they can cause more serious problems in the lungs, intestines, liver, kidneys, hormone-making glands, or other organs.
Many other drugs that target either PD-1 or PD-L1 are now being tested in clinical trials as well, both alone and combined with other drugs (see What’s new in cancer immunotherapy research?).
Drugs that target CTLA-4
CTLA-4 is another protein on some T cells that acts as a type of “off switch” to keep the immune system in check.
Ipilimumab (Yervoy) is a monoclonal antibody that attaches to CTLA-4 and stops it from working. This can boost the body’s immune response against cancer cells.
This drug is used to treat melanoma of the skin. It is also being studied for use against other cancers.
Because ipilimumab affects the immune system, it can sometimes cause serious or even life-threatening side effects. In fact, compared to drugs that target PD-1 or PD-L1, serious side effects seem to be more likely with ipilimumab.
Last Medical Review: July 23, 2015 Last Revised: March 23, 2017