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What is CAR-T therapy? An expert explains

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Updated 30 Jul 2018

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

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. 

We asked Professor Karl Peggs, Scientific Director of the NIHR BTRU in Stem Cells and Immunotherapies, 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. 

CAR-T - how it works

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. Professor Karl Peggs is leading our 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. 

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

Currently, CAR-T therapy in the UK is only available through clinical trials, although the National Institute of Clinical Excellence (NICE)is currently considering the evidence to decide whether to approve it for commissioning on the NHS in England. 

The NICE appraisals will focus on two different manufacturers’ versions of CAR-T, one for treating adults with DLBCL, mediastinal B-cell lymphoma and follicular lymphoma and the other for treating adults with DLBCL and children and young people (aged 3-25) with relapsed or refractory B-cell lymphoblastic leukaemia. The decisions are likely to be published by NICE in the autumn. 

In the United States, CAR-T therapy is approved for some forms of aggressive, hard to treat non-Hodgkin lymphoma that has not responded to standard therapy or has relapsed after at least two other kinds of treatment failed. It is also been approved for use in children and young adults (up to the age of 25) who have acute lymphoblastic leukaemia (ALL)that has returned, or is resistant to treatment. The treatment is expensive with the cost in the US reported at $475,000 (£340,000) per patient.

The Chief Executive of NHS England, Simon Stevens, said in an interview with The Guardian recently: 

“Preparations are under way to make CAR-T, one of the most innovative treatments that has ever been offered on the NHS, available to patients, but manufacturers need to set fair and affordable prices so treatments can be made available to all who need them1.” 

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.