Checkpoint inhibitors

Checkpoint inhibitors are drugs which 'take the brakes off' the immune system, allowing tumour cells to be destroyed.

How Checkpoint inhibitors work

Normal cells in your body have particular proteins on their surface that the immune system recognises as not dangerous, so your body's immune system doesn't attack them. As these proteins effectively hold the immune system in check, they are called 'checkpoint proteins'.

However, tumour cells can sometimes fool the immune system by also producing these checkpoint proteins, preventing the immune system from recognising them as dangerous and from attacking them.

'Checkpoint inhibitors' are drugs that block these checkpoint proteins, so the tumour cells now become visible to the immune system and the 'brakes' are taken off the immune system, allowing the tumour cells to be destroyed.

The down-side of this, however, is that it also takes the brakes off the immune system attacking your normal cells. This can lead to various side-effects, which can occur at any time and can affect many different organs.

Side Effects

The most common side-effects are rash, diarrhoea, reduced levels of thyroid hormone, and fatigue. More severe side-effects can be due to inflammation of the lung, intestines or liver, hormonal abnormalities, and kidney, heart, or neurologic problems.

If the side-effects are mild, it may be possible to continue using the checkpoint inhibitors, but you will need to be closely monitored.

If the side-effects are more than mild, you will have to stop using the checkpoint inhibitors. This may be temporarily or may be permanently, depending on the severity of your reaction to them. You may also have to take corticosteroids for at least 6 weeks to reduce the inflammation.

Immunotherapy clinical trials for brain tumours

So far only a few checkpoint inhibitors have gained approval (in some countries only) and these are for use with other tumours/cancers, such as melanoma, Hodgkin's lymphoma and urothelial cancer.

However, some are in clinical trials or studies for brain tumours – for example:

• Ipilimumab
• Pembrolizumab
• Nivolumab
• Pidilizumab

Information about clinical trials can be found at ClinicalTrials.gov

It should also be remembered that many cancer patients don't respond to immune checkpoint inhibitors. There is, however, growing interest in combining these agents with chemotherapy, radiotherapy, and other treatments to boost their effectiveness, such as the one listed above - ipilimumab with bevacizumab (Avastin) in glioblastoma.