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What is CAR-T therapy? An expert explains

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Updated 18 Oct 2018

CAR-T therapy has caused a huge amount of excitement because it has meant some people with the prospect of only having months to live, are now cancer free. CAR-T therapy could offer people with certain hard-to-treat blood cancers the chance for long-term survival, or even a cure.

A word with Professor Karl Peggs

Professor Karl Peggs is Scientific Director of the National Institute for Health Research (NIHR) Blood and Transplant Research Unit in Stem Cells and Immunotherapies. We ask him what CAR-T therapy means for people living with blood cancer.

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

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

The National Institute of Clinical Excellence (NICE) has been considering the evidence as to whether to approve CAR-T for use on the NHS in England.

On 5 September 2018, NHS England announced that it would be funding CAR-T for people aged under 25 years old with B cell acute lymphoblastic leukaemia (ALL) and said this would be available in ‘weeks’. We expect that this would only be suitable for between 15 and 25 children and young people.

On 5 October 2018, NHS England announced that it would also be funding a type of CAR-T called axicabtagene ciloleucel (also known as Yescarta) to treat adult patients with DLBCL and primary mediastinal B-cell lymphoma after two or more previous therapies have failed. Trials indicate that the therapy could potentially cure 40% of patients.

A final decision on a similar CAR-T drug called Kymriah, also for the treatment of DLBCL, is expected in autumn/winter 2018.

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 considering the evidence as to whether CAR-T should be available for people with relapsed or refractory diffuse large B-cell non-Hodgkin lymphoma. 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.