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What is CAR-T therapy? An expert explains

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Updated 28 Nov 2018

CAR-T therapy is a completely new type of therapy that uses the immune system to kill cancer cells.

In some cases it has cured people where all other treatments have failed. Professor Karl Peggs, Scientific Director of the  National Institute for Health Research (NIHR) Blood and Transplant Research Unit in Stem Cells and Immunotherapies explains more.

How does CAR-T therapy work? 

"T-cells are a type of immune cell that help the body fight infection by seeking out viruses, bacteria and parasites, and then killing them. T-cells also look for and destroy abnormal cells, such as cancer cells. Researchers have found that T-cells can be taken out of a patient’s body and genetically modified to boost their ability to recognise and kill specific cancer cells. 

"Researchers do this by collecting T-cells from the patient’s blood, which are then modified in a laboratory to produce special structures called chimeric antigen receptors (CARs) on their surface. When these CAR-T cells are given back to the patient as an infusion, the new receptors enable them to recognise specific proteins on the cancer cells and kill them. 

"As CAR-T therapy is made up of living T-cells, they are able to circulate around the body just like any other blood cell. As result, CAR-T is a dynamic therapy, which reacts when it comes into contact with the target cancer cells. When this happens, the CAR-T cells release biological substances called cytokines that recruit other immune cells to join with them to kill the cancer cells. 

"This allows the CAR-T cells to educate the immune system to recognise and kill cancer cells. 

"Research has shown that CAR-T cells can remain in the body and continue to be active for a long period of time. So unlike most cancer treatments, which are taken continuously, CAR-T therapy is designed to be a one-time treatment."

Who can have CAR T-cell therapy? 

"CAR-T therapy is designed for people with advanced or progressing blood cancers, who have limited treatment options open to them. It’s suitable for people with certain types of blood cancer who initially responded to treatment, but then relapsed (the cancer returned). It can also help those whose blood cancer is not responding to treatment (refractory or resistant disease)."

What are the possible side effects of CAR-T therapy? 

"CAR-T therapy is still very new and can cause some serious side effects, and is a major reason why this treatment is done only in hospitals that have an expert team to manage these. Sometimes, CAR-T therapy can trigger serious conditions, usually within five days of the infusion. Cytokine release syndrome can occur when immune cells activated by the treatment release an excessive amount of cytokines, resulting in a type of immune reaction similar to a severe infection. 

"This can lead to flu-like symptoms, such as: high fever and/or chills; racing heart beat; drop in blood pressure; and difficulty breathing. Neurological side effects can also occur, causing the patient to experience headaches, confusion, difficulty understanding language and speaking, or stupor. 

"However, in almost all cases, these side effects completely resolve within days to weeks and do not return."

What CAR-T therapy trials for blood cancer are happening in the UK? 

"Bloodwise is one of a small number of organisations funding CAR-T therapy trials. I am leading University College London's Bloodwise-funded COBALT trial, which is looking at the safety of a CAR-T therapy for people with an aggressive type non-Hodgkin lymphoma called diffuse large B cell lymphoma (DLBCL). The CAR-T therapy in this trial targets a protein called CD19 that’s found on the surface of some lymphoma cells. It’s a ‘bridging treatment’ for people with DLBCL, to get them into remission before a donor stem cell transplant."

Will CAR-T therapy cure blood cancer? 

"CAR-T is an exciting new treatment which has considerably changed the outlook for some people living with blood cancer. However, it is not appropriate for all types of blood cancer, and not everyone with those cancers where it is available responds to this treatment. Why certain patients respond while others don’t is not well understood, and more research is needed.

"For those that do respond, because CAR-T therapy is a new treatment, we don’t have a complete picture on the long term side effects, and how long people’s response lasts."

CAR-T - how it works

About the CAR-T research Bloodwise funds

We’re currently funding research on a potential CAR-T therapy for acute lymphoblastic leukaemia that doesn’t need to be tailored to each person, and a clinical trial looking at whether CAR-T can help people with relapsed or treatment-resistant diffuse large B cell lymphoma become strong enough to have a stem cell transplant. In the past, we’ve also funded research on developing CAR-T therapy for myeloma and lymphoma.

When will CAR-T cell therapy be available in England? 

In England the National Institute of Clinical Excellence (NICE)  approves drugs and treatments for use on the NHS. There are currently two types of CAR-T treatment that have been developed by two different pharmaceutical companies. They are called Yescarta® (from Gilead) and Kymriah® (from Novartis). NICE has approved the use of these CAR-T treatments in the following ways:

  • For children and young people (up to age 25) with B-cell acute lymphoblastic leukaemia, if other treatments have not worked, NICE has approved the use of Kymriah® CAR-T therapy, via the Cancer Drugs Fund.
  • For adults with diffuse large B-cell lymphoma (DLBCL) or primary mediastinal B-cell lymphoma (PMBCL), if other treatments have not worked, NICE has approved the use of Yescarta® CAR-T therapy, via the Cancer Drugs Fund.

NICE has also assessed Kymriah® CAR-T therapy for adults with diffuse large B-cell lymphoma (DLBCL) where other treatments have not worked, but the outcome isn’t yet public.

The first wave of NHS hospitals working towards providing these treatments are in Birmingham, Bristol, London, Manchester and Newcastle.

When will CAR-T cell therapy be available in Scotland? 

The Scottish Medicines Consortium, which decides whether drugs and treatments should be available on the NHS in Scotland, is currently assessing the evidence of the two CAR-T therapies (Kymriah and Yescarta). A decision is expected later in 2018.

When will CAR-T cell therapy be available in Wales and Northern Ireland? 

Services for children with cancer are commissioned by the Welsh Health Specialised Services Committee on behalf of health boards in Wales.

The Government recently stated that ‘if NICE recommends the therapy for routine use, then it will be made available to patients in Wales within 60 days’.

It is unclear as to when CAR-T might be available in Northern Ireland.