Checkpoint inhibitors are used to treat cancers such as melanoma skin cancer and lung cancer. Researchers are also looking at them in clinical trials for other types of cancer.
You might also hear these drugs called CTLA-4 inhibitors, PD-1 inhibitors and PD-L1 inhibitors. CTLA-4, PD-1 and PD-L1 and the names of the checkpoint proteins that are blocked.
What are they?
Checkpoint inhibitors are a type of immunotherapy. They block proteins that stop the immune system from attacking the cancer cells.
Cancer drugs do not always fit easily into a certain type of treatment. This is because some drugs work in more than one way and belong to more than one group.
Checkpoint inhibitors are also described as a type of monoclonal antibody or targeted treatment.
How checkpoint inhibitors work
Our immune system protects us from disease, killing bacteria and viruses. One main type of immune cell that does this is called a T cell.
T cells have proteins on them that turn on an immune response and other proteins that turn it off. These are called checkpoints. Some checkpoint proteins help tell T cells become active, for example when an infection is present. But if T cells are active for too long, or react to things they shouldn’t, they can start to destroy healthy cells and tissues. So other checkpoints help tell T cells to switch off.
Some cancer cells make high levels of proteins. These switch off T cells, when they should really be attacking the cancer cells. So the cancer cells manage to push a stop button on the immune system. The T cells can no longer recognise and kill cancer cells.
Drugs that block checkpoint proteins are called checkpoint inhibitors. They stop the proteins on the cancer cells from pushing the stop button. This turns the immune system back on and the T cells are able to find and attack the cancer cells.
Our immune system protects us from disease, killing bacteria and viruses.
It also helps fight cancer.
A T cell is one type of immune cell that does this.
T cells have proteins on them that turn the immune system on when it needs to fight infection….
and other proteins that turn the immune system off when it is no longer needed. These are called checkpoints.
Cancer cells can trick the immune system by turning the T cells off ….
stopping them from recognising and attacking the cancer cells.
Drugs called checkpoint inhibitors turn the T cells back on ....
so they can recognise and attack the cancer cells.
For more information about checkpoint inhibitors click here.
These drugs block different checkpoint proteins including CTLA-4, PD-1 and PD-L1 (programmed death ligand 1). CTLA-4 and PD-1 are found on T cells. PD-L1 are on cancer cells.
Checkpoint inhibitors that block PD-1 include:
- nivolumab (Opdivo)
- pembrolizumab (Keytruda)
Nivolumab and pembrolizumab are treatments for some people with:
- melanoma skin cancer
- Hodgkin lymphoma
- non small cell lung cancer
- cancer of the urinary tract (urothelial cancer)
The urinary tract includes the:
- centre of the kidney (renal pelvis)
- tube that takes urine from the kidney to the bladder (ureter)
- tube that drains urine from the bladder and out of the body
Ipilimumab (Yervoy) is a checkpoint inhibitor drug that blocks CTLA-4. It is a treatment for advanced melanoma.
A drug called atezolizumab (also known as MPDL3280A) blocks PD-L1.
Atezolizumab is a treatment for some people with lung cancer and urothelial cancers. Urothelial cancers include bladder cancer and cancer of the ureter. The ureter is the tube that carries urine from the bladder to outside the body.
Atezolizumab is also in clinical trials for uroltheial cancers and breast cancer in the UK.
When you might have these drugs
Ask your doctor if these drugs are suitable for you. Whether you can have this treatment depends on your type of cancer. It might also depend on:
- the stage of your cancer
- whether you have already had certain treatments
To find out if you can have pembrolizumab for non small cell lung cancer, you need to have your cancer cells tested. To have this PD-1 inhibitor for lung cancer, you need to have large amounts of the PD-L1 protein on your cancer cells. This is called PL-L1 positive cancer.
This testing does not apply to all checkpoint inhibitors. Your doctor or specialist nurse can tell you if this applies to you.
You might be offered checkpoint inhibitors as part of a clinical trial. Or you could ask your doctor whether there are any trials that you could take part in.
How you have treatment
You usually have these drugs as a treatment through a drip into your bloodstream.
These drugs boost all the immune cells, not just the ones that target cancer. So the overactive T cells can cause side effects. These include:
- tiredness (fatigue)
- feeling or being sick
- dry, itchy skin, skin rash
- loss of appetite
- breathlessness and a dry cough, caused by inflammation of the lungs
These drugs can also disrupt the normal working of the liver, kidneys and hormone making glands (such as the thyroid). You have regular blood tests to check for this.
Some of these side effects can be serious. Your medical team will talk through the possible side effects so you know what to look out for. Tell your doctor or nurse if you have any side effects so they can treat them as soon as possible.
Side effects, such as diarrhoea, can be serious. And you are also likely to have worse side effects if you have ipilimumab and nivolumab together. You might have these 2 drugs if you have advanced melanoma.