The immune system is our unsung hero when it comes to staying healthy and sickness-free.
Without us even noticing, it mounts round-the-clock defences against rogue organisms (everything from cold and flu viruses to harmful bacteria and even cancer) to prolong our survival for as long as possible.
But sometimes – and for reasons scientists are still struggling to fathom, despite decades of research – the body’s defence mechanism goes haywire and turns against us, leaving a trail of incurable, life-changing diseases in its wake.
Called autoimmune disorders, these include type 1 diabetes (where the rogue immune response damages insulin-producing cells in the pancreas); rheumatoid arthritis (affecting joints such as the knees, wrists and fingers which become painful and swollen); multiple sclerosis (MS, where the immune system destroys the protective coating around nerves that control sensation and movement – causing weakness and immobility) and inflammatory bowel disease (where the abnormal response leads to damaging inflammation in the bowel, causing pain, diarrhoea and weight loss).
There are at least 80 more – and autoimmune disorders affect an estimated four million people in the UK, leaving many at risk of life-changing consequences as these conditions are difficult to treat.
But exciting new research suggests a type of treatment – called CAR T-cell therapy (or chimeric antigen receptor T-cell therapy and originally developed to fight certain forms of cancer) – could potentially stop all of these incurable disorders in their tracks by ‘resetting’ the immune system so it ceases its attacks on healthy tissue.
Current medications merely control symptoms, rather than tackling the underlying disease
Some experts predict it could be one of the biggest advances in treatment for decades.
‘CAR T-cell therapy was a big breakthrough in the treatment of cancer and it could be for many autoimmune conditions as well,’ says Professor Maria Leandro, a consultant rheumatologist at University College London Hospital (UCLH) and one of the UK’s leading researchers in its use for autoimmune illnesses.
‘In theory, it could work for almost any of these conditions.’
CAR T-cell therapy, which was approved in the UK for certain types of leukaemia in 2018, involves using a sample of blood from the patient and harvesting T-cells from it in the laboratory.
T-cells are a type of defender cell that patrol the bloodstream, destroying any rogue organisms or cells. But it can be difficult for them to tell the difference between a cancer cell and a healthy one. One way around this is to tinker with T-cells by exposing them to a drug that alters their DNA, so they produce a protein called chimeric antigen receptor (CAR). This protein can more easily detect cancer cells.
Once a T-cell becomes a CAR T-cell, it’s reproduced in large numbers in the lab and injected a few weeks later back into the patient’s body. These drugs – which include Kymriah (also called tisagenlecleucel) – have transformed the treatment of blood cancers, with some patients told they just had months to live finding themselves in complete remission.
Now UK scientists are hoping the same treatment could work wonders for autoimmune conditions – for which current medications merely control the symptoms, rather than tackle the underlying disease.
Instead of attacking cancer cells, in this case the modified T-cells would target B-cells, another type of immune cell which have got their wires crossed and are attacking the body instead of defending it. Researchers at UCLH – including Professor Leandro – and Manchester Royal Infirmary are testing CAR T-cell therapy in patients with lupus, an autoimmune illness that affects almost 70,000 people in the UK and causes joint and muscle pain, skin rashes and extreme fatigue.
Many lupus patients end up on a lifelong cocktail of potent drugs that can reduce the worst of the symptoms but can have unpleasant side-effects – steroids, for example, can cause swelling, weight gain and osteoporosis.
Last month, three UK patients underwent CAR T-cell therapy for lupus after a 15-year-old girl in Germany was given the treatment as a last resort – when all other drugs had failed – and became symptom-free within months as the therapy ‘reset’ her immune system and freed her of the need to take any drugs at all.
Although it’s too early to say if it has worked in the UK volunteers, the treatment (which is being trialled in 12 patients) is regarded by many as the closest science has so far come to finding a cure for lupus. ‘The data from the German trials suggest some patients were still in remission three years after a single CAR T-cell treatment,’ Professor Leandro told Good Health.
Professor Maria Leandro believed that since CAR T-cell therapy was a big breakthrough in the treatment of cancer, it could be for many autoimmune conditions as well
So if it works for lupus, can it also work in other related illnesses? ‘In theory, yes,’ says Professor Leandro. ‘There is a lot of research showing that if we deplete the harmful B-cells then we can reset the immune system and there are several other diseases in which we would expect it to work – including rheumatoid arthritis, type 1 diabetes and multiple sclerosis.’
However, she warns that CAR T-cell therapy cannot reverse damage an autoimmune disorder may have already caused. ‘But we know that in many of these diseases it’s possible to detect autoantibodies [destructive proteins triggered by the harmful B-cells] in the blood before the disease sets in.’
That might in future mean regularly screening those at high risk of illness – possibly because of a family history, she adds.
‘Even if we were only able to postpone the onset of the disease by three to five years with CAR T-cell therapy, that could prevent a lot of the damage to organs and tissues that make these conditions so unpleasant,’ says Professor Leandro.
Early research on mice suggests the therapy might also help tackle type 1 diabetes. In a 2020 study at Harvard University, CAR T-cell therapy was shown to block damage to the pancreas and protect it against the immune system’s misguided attacks.
Meanwhile, volunteers aged 18 to 60 are being sought for a trial at UCLH and Manchester Royal Infirmary to see if CAR T-cell therapy will switch off their multiple sclerosis. The trial is due to run until 2027.
And at least 60 other clinical trials around the world are being set up to investigate the effects of the drugs on a wide range of autoimmune conditions. The results will be eagerly awaited, as some studies suggest autoimmune illnesses are on the increase globally, though nobody is sure why.
The charity Diabetes UK, for example, says it can’t be down to genes alone, as the increase is happening too rapidly for it to be the result of changes in our DNA.
It is focusing its research instead on potential triggers, such as a family of viruses called human enteroviruses, which it says appear to be a likely culprit.
They are spread through poor hygiene and can cause symptoms ranging from flu-like illness to chest infections. One theory is these viruses somehow expose insulin-producing cells in the pancreas to the immune system in such a way that it mistakes them for a foreign organism and launches an all-out attack.
But for all its promise, CAR T-cell therapy is not without its risks.
Side-effects can include something called cytokine release syndrome – where the immune system reacts to treatment by causing rapid heartbeat and difficulty breathing – to temporary confusion, difficulty speaking and seizures.
‘In autoimmune diseases, we don’t know yet what the long-term effects are regarding safety and effectiveness,’ says Dr Ulrich Blache, an expert in cellular and molecular biology at the Fraunhofer Institute for Cell Therapy and Immunology in Germany.
‘And the safety bar will certainly be higher for the less severe autoimmune diseases. But it is conceivable that the more common ones – type 1 diabetes, rheumatoid arthritis and multiple sclerosis – could be targeted using CAR T-cells in the future.’
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