Analysis: the new groundbreaking treatment uses the patient's own immune cells to fight their cancer
St James' Hospital Dublin recently announced that a new form of cancer treatment called CAR T-cell therapy is now available to patients with lymphoma. Called 'chimeric antigen receptor’ (CAR) T-cell therapy, this treatment uses the patient’s own immune cells to fight their cancer. Immune cells are isolated from blood, trained in a lab to be able to recognise cancerous cells and reinfused into the patient as a ‘living drug’, where they can seek and destroy cancer.
How exactly do CAR T-cells work?
These cells work by exploiting how the immune system normally operates. When some foreign invader such as a virus enters the body, immune cells use receptors to ‘see’ patterns on the invader’s surface, like reading a barcode. This pattern recognition tells the immune cells that this invader is not usually found in the body and is therefore potentially dangerous.
We need your consent to load this rte-player contentWe use rte-player to manage extra content that can set cookies on your device and collect data about your activity. Please review their details and accept them to load the content.Manage Preferences
From RTÉ Radio 1's Morning Ireland, Sinead Spain reports on the groundbreaking CAR T cell cancer therapy now available in Ireland
This danger signal triggers immune cells to become activated and destroy the invader. One type of immune cell particularly adept at killing harmful invaders is called a T-cell. T-cells protect us from all kinds of pathogens and developing cancers, and can even remember invaders previously encountered. T-cells are the type of immune cell that HIV attacks, and loss of T-cells is what causes AIDS, where the body’s ability to fight infection or cancer is severely compromised.
What makes cancer so tricky to fight is that the ‘invader’ is our own cells. Cancer arises from any cell that has lost the ability to control its growth. Usually, these abnormal cells are recognised and killed off by the immune system before they can become dangerous, but sometimes cancer cells don’t look different enough from normal cells to trigger a danger signal.
This immunological blind spot is where CAR T-cells can intervene. The immune recognition system can be tweaked by genetically engineering T-cells to be able to recognise patterns specific to cancer cells. This is achieved by introducing genes to create new T-cell receptors, the immune system’s barcode readers. This arms your killer cells with new pattern recognition equipment, able to trigger an immune attack once a cancer cell is encountered.
We need your consent to load this rte-player contentWe use rte-player to manage extra content that can set cookies on your device and collect data about your activity. Please review their details and accept them to load the content.Manage Preferences
From RTÉ 2fm's Jennifer Zamparelli show, interview with 15-year old Alex McEleney who is receiving CAR T-cell therapy treatment
How do CAR T cells compare with other cancer treatments?
CAR T-cell therapy is relatively new. The first CAR T-cell drug, called tisagenlecleucel (Kymriah), was approved by the FDA in the US in 2017, to treat children with a form of acute lymphoblastic leukaemia. Currently, there are six approved CAR T-cell therapies, all of which are used to treat adults and children with certain blood cancers. Traditional cancer treatments such as chemotherapy and radiotherapy remain first line treatment choices, but so-called ‘immunotherapies’ such as CAR T-cells offer new hope to patients when these standard treatments fail.
A clinical trial called the ELARA trial evaluated the efficacy of CAR T-cell therapy on 97 patients with follicular lymphoma which had failed at least two prior treatments. 69% of those given tisagenlecleucel showed a disappearance of all signs of cancer, compared to 37% of patients given usual care. Patients given tisagenlecleucel were also 1.4 times more likely to be alive a year after treatment. Importantly, a long term follow-up trial (the JULIET trial with 115 patients) showed that the beneficial effects of a single tisagenlecleucel treatment were durable, with 39% of patients remaining in complete remission three years on.
So why isn’t CAR T cell therapy a first line treatment choice?
Despite the buzz around CAR T-cell therapy, this approach is currently much more labour-intensive and expensive than normal therapies. Cell engineering requires sterile, specialist conditions and takes time to engineer cells.
There are currently over a thousand clinical trials involving CAR T-cells ongoing worldwide.
Another drawback is side effects, which can be potent and debilitating, requiring hospital monitoring. Documented side effects include cytokine release syndrome (reported in almost 50% of patients), anaemia (39% of patients), and neurological disturbances (37%) involving severe confusion, seizure-like events and impaired speech. Drugs are available to manage these side effects, though it is recommended that only patients fit enough to endure the potential side effects receive CAR T-cell treatment. The longer term effects of this treatment also remain to be seen, on a greater number of patients.
What’s next for CAR T cell therapy?
CAR T cells can theoretically be created to target many more cancer types, and even other diseases. Once danger patterns specific enough for problem cells can be identified, new receptors can be engineered. There are currently over a thousand clinical trials involving CAR T-cells ongoing worldwide.
Current research aims to improve recognition for more cancer types, to lower toxicity and improve efficacy. Other types of killer immune cells are also being engineered to express chimeric antigen receptors and these don’t need to be the patient’s own cells, meaning quicker treatment by cutting out the time needed to train cells. If current trends continue, more breakthroughs are on the horizon for this new class of living drugs, our latest weapon in the fight against cancer.
The views expressed here are those of the author and do not represent or reflect the views of RTÉ
