Checkpoint inhibitor drugs are an advance in cancer treatment that function as a type of immunotherapy, harnessing the body’s own immune system to combat cancer cells. Unlike traditional treatments like chemotherapy that directly kill cancer cells, checkpoint inhibitors empower the immune system to recognize and eliminate them. This therapy is administered intravenously, with sessions lasting between 30 and 60 minutes. The total number of sessions a patient receives varies depending on the specific cancer and drug used.
How Checkpoint Inhibitors Work
The immune system has natural safeguards called checkpoints, which prevent its cells from attacking the body’s healthy tissues. These checkpoints are proteins on the surface of immune cells, particularly T-cells, which identify and destroy foreign or abnormal cells. A primary function of these checkpoints is to act as an “off” switch, deactivating the T-cell to avoid excessive inflammation or autoimmune reactions.
Some cancer cells exploit this protective mechanism to evade destruction. These tumor cells produce proteins on their surface that bind to the checkpoint proteins on T-cells. For example, many cancer cells have high levels of a protein called PD-L1, which connects with a checkpoint protein called PD-1 on T-cells. This interaction signals that the cancer cell is healthy, turning the T-cell off and allowing the cancer to grow.
Checkpoint inhibitor drugs disrupt this deceptive signaling. These medications are a type of monoclonal antibody, which are lab-produced proteins designed to target specific molecules. They work by blocking either the checkpoint proteins on T-cells (like PD-1) or the corresponding proteins on cancer cells (like PD-L1). This blockade prevents the cancer cell from deactivating the T-cell, “releasing the brakes” on the immune response so T-cells can recognize and attack the cancer.
Types of Checkpoint Inhibitor Drugs
Checkpoint inhibitors are categorized based on the specific checkpoint protein they target. The main classes of these drugs are PD-1 inhibitors, PD-L1 inhibitors, and CTLA-4 inhibitors.
PD-1 Inhibitors
PD-1 inhibitors block the PD-1 protein on the surface of T-cells, which prevents cancer cells from deactivating them. This restores the T-cells’ ability to identify and kill tumor cells. Commonly used PD-1 inhibitors include Pembrolizumab (Keytruda), Nivolumab (Opdivo), and Cemiplimab (Libtayo).
PD-L1 Inhibitors
PD-L1 inhibitors target the PD-L1 protein on the surface of some tumor cells. By blocking this protein, the drugs prevent it from binding to the PD-1 protein on T-cells, which keeps the immune system active against the cancer. Drugs in this category include Atezolizumab (Tecentriq), Avelumab (Bavencio), and Durvalumab (Imfinzi).
CTLA-4 Inhibitors
CTLA-4 is another checkpoint protein on T-cells that acts as a brake on the immune response. By blocking the CTLA-4 protein, these drugs allow T-cells to remain active and fight cancer cells. Ipilimumab (Yervoy) is the primary drug in this class and is used to treat certain cancers.
Cancers Treated With Checkpoint Inhibitors
Checkpoint inhibitors are used for a wide variety of cancers, particularly those that are advanced or have metastasized. One of the first successes for these drugs was in treating melanoma, where they have improved patient outcomes. Non-small cell lung cancer is another area where these inhibitors have become a standard part of treatment.
Beyond melanoma and lung cancer, these therapies are approved for other malignancies. Kidney and bladder cancer are frequently treated with checkpoint inhibitors. Hodgkin lymphoma has also responded well to this immunotherapy, as have certain types of breast, cervical, and head and neck cancers.
The list of cancers treated with these drugs is growing as research explores their effectiveness against other tumors, such as sarcomas and different forms of lymphoma. Before prescribing a checkpoint inhibitor, doctors may test the tumor for biomarkers like PD-L1 expression. This testing helps predict if the treatment is likely to be effective for the patient’s cancer.
Immune-Related Side Effects
Because checkpoint inhibitors stimulate the immune system, their side effects differ from those of traditional chemotherapy. The main complications are immune-related adverse events (irAEs), which occur when the activated immune system mistakenly attacks healthy tissues. This can cause inflammation in various organs.
These side effects vary depending on the part of the body affected. Skin-related issues like rashes and itching are common. If the intestines are targeted, patients may experience diarrhea or colitis, which is inflammation of the colon.
The endocrine system, which includes hormone-producing glands, can also be affected, resulting in conditions like thyroid problems or hepatitis (liver inflammation). In rare cases, serious complications such as myocarditis (inflammation of the heart muscle) can occur. Patients should report any new symptoms to their healthcare team promptly, as managing these side effects is part of the treatment process.