Introduction
Immune checkpoint inhibitors are a type of immunotherapy that are increasingly being used to treat certain types of cancer, as an alternative to cytotoxic chemotherapy. In contrast to therapies such as chemotherapy and tumour-targeted drugs that directly affect the growth and proliferation of tumour cells, these targeted treatments harness the body’s natural anti-cancer immune response. They boost its ability to attack and destroy the cancer cells.
Mechanism of action
T-cells are an important part of our immune system which help destroy cancer cells. Some cancer cells make high levels of proteins that turn T-cells off. Checkpoint inhibitors block this process and reactivate and increase the body’s own T-cell population, enhancing the immune systems own ability to recognise and fight cancer cells.
Indications
Types:
The proteins CTLA-4 and PD-1 are found on T-cells and PD-L1 are found on cancer cells.
- Ipilimumab (Yervoy) is a checkpoint inhibitor that blocks CTLA-4 (cytotoxic T lymphocyte-associated protein 4). It is a treatment for advanced melanoma.
- Nivolumab (Opdivo) and pembrolizumab (Keytruda) blocks PD-1 (programmed cell death protein 1). These are treatments for melanoma, Hodgkin's lymphoma, non-small cell lung cancer and urological cancers.
- Atezolizumab, Avelumab and Durvalumab block PD-L1 and is used to treat lung cancer and urothelial cancer. It is also undergoing trials as a treatment for breast cancer.
The proteins CTLA-4 and PD-1 are found on T-cells and PD-L1 are found on cancer cells.
Adverse effects
This mechanism of action of these drugs can result in side effects termed 'Immune-related adverse events' that are inflammatory and autoimmune in nature. This is because all immune cells are boosted by these drugs, not just the ones that target cancer. The over-active T-cells can produce side effects such as:
Management of such side effects reflects the inflammatory nature, often involving corticosteroids.
- Dry, itchy skin and rashes (most commonly)
- Nausea and vomiting
- Decreased appetite
- Diarrhoea
- Tiredness and fatigue
- Shortness of breath and a dry cough.
Management of such side effects reflects the inflammatory nature, often involving corticosteroids.
Monitoring
It is important to monitor liver, kidney and thyroid function as these drugs can affect these organs.