The immune system is our unsung hero when it comes to staying healthy and disease-free.
Without us even noticing, a defense mechanism is mounted 24 hours a day against malicious 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 that scientists still struggle to understand despite decades of research – the body’s defenses go haywire and turn against us, leaving a trail of incurable, life-altering diseases in the wake.
These so-called autoimmune diseases include type 1 diabetes (where the malignant 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 covering around the nerves that control sensation and movement – causing weakness and immobility) and inflammatory bowel disease (where the abnormal response leads to harmful inflammation in the intestines, causing pain, diarrhea and causes weight loss).
There are at least 80 more – and autoimmune diseases affect an estimated four million people in Britain, leaving many at risk of life-changing consequences as these conditions are difficult to treat.
But exciting new research suggests that a type of treatment – called CAR T-cell therapy (or chimeric antigen receptor T-cell therapy and originally developed to fight certain cancers) – could potentially stop all these incurable conditions in their tracks by ‘resetting the of the disease’. ‘ the immune system so that it stops its attacks on healthy tissue.
Current medications only control symptoms, rather than addressing the underlying disease
Some experts predict this could be one of the biggest advances in treatment in decades.
“CAR T-cell therapy was a major breakthrough in the treatment of cancer and could also be for many autoimmune diseases,” says Professor Maria Leandro, rheumatologist at University College London Hospital (UCLH) and one of Groot’s leading researchers. -Britain. in its use for autoimmune diseases.
“In theory, it could work for almost all of these conditions.”
CAR T-cell therapy, which was approved in Britain in 2018 for certain forms of leukemia, involves using a patient’s blood sample and harvesting T cells from it in the laboratory.
T cells are a type of defense cells that patrol the bloodstream and destroy any malignant organisms or cells. But it can be difficult for them to tell the difference between a cancer cell and a healthy cell. One way around this is to tinker with T cells by exposing them to a drug that changes their DNA so they produce a protein called chimeric antigen receptor (CAR). This protein can detect cancer cells more easily.
Once a T cell becomes a CAR T cell, it is reproduced in large numbers in the laboratory and injected back into the patient’s body a few weeks later. These drugs – including Kymriah (also called tisagenlecleucel) – have transformed the treatment of blood cancer, with some patients told they had only months to live and were in complete remission.
Now British scientists hope the same treatment could work wonders for autoimmune diseases – where current drugs merely control symptoms, rather than tackling the underlying disease.
Instead of attacking cancer cells, the modified T cells in this case would target B cells, another type of immune cell that have their wires crossed and attack the body instead of defending it. Researchers from UCLH – including Professor Leandro – and Manchester Royal Infirmary are testing CAR T-cell therapy in patients with lupus, an autoimmune disease that affects almost 70,000 people in Britain and causes joint and muscle pain, rashes and extreme fatigue.
Many lupus patients end up on a lifelong cocktail of powerful medications that can reduce the worst symptoms but can have unpleasant side effects – for example, steroids can cause swelling, weight gain and osteoporosis.
Last month, three British 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’ and freed her immune system her from the need to take medications.
Although it is too early to say whether it has worked in British volunteers, the treatment (being trialled on 12 patients) is considered by many to be the closest science has yet come to finding a cure for lupus. ‘The data from the German studies suggest that 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 major breakthrough in cancer treatment, this could also apply to many autoimmune diseases
So if it works for lupus, could it also work for other related diseases? “In theory, yes,” says Professor Leandro. ‘There is a lot of research showing that if we deplete the harmful B cells we can reset the immune system and there are several other diseases where we expect it to work – including rheumatoid arthritis, type 1 diabetes and multiple sclerosis. ‘
However, she cautions that CAR T-cell therapy cannot reverse the damage that an autoimmune disease has already caused. ‘But we know that in many of these diseases it is possible to detect autoantibodies (destructive proteins activated by the harmful B cells) in the blood before the disease manifests.’
That could mean in the future that people at high risk of disease are regularly screened – possibly because of a family history, she adds.
“Even if we could delay the onset of the disease for just three to five years with CAR T-cell therapy, it could prevent much of the damage to organs and tissues that make these conditions so unpleasant,” says Professor Leandro.
Early research in mice suggests the therapy may also help tackle type 1 diabetes. A 2020 study at Harvard University found that CAR T-cell therapy blocks damage to the pancreas and protects it from 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 knock out their multiple sclerosis. The trial runs until 2027.
And at least 60 other clinical trials are being set up worldwide to investigate the drugs’ effects on a wide range of autoimmune diseases. The results are eagerly awaited, as some studies suggest autoimmune diseases are on the rise worldwide, although no one knows for sure why.
For example, the charity Diabetes UK says it cannot be down to genes alone, as the increase is happening too quickly to be the result of changes in our DNA.
It is instead focusing its research on possible triggers, such as a family of viruses called human enteroviruses, which it says appear to be a likely culprit.
They are spread by poor hygiene and can cause symptoms ranging from flu-like illnesses to respiratory infections. One theory is that 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 promises, CAR T-cell therapy is not without risks.
Side effects can include so-called cytokine release syndrome – where the immune system responds to treatment by causing a rapid heart rate and breathing difficulties – to temporary confusion, speech problems and seizures.
“In autoimmune diseases, we do not yet know what the long-term effects are in terms of 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 for the less serious autoimmune diseases the safety bar will certainly be higher. But it is conceivable that the most common forms – type 1 diabetes, rheumatoid arthritis and multiple sclerosis – could be tackled in the future using CAR T cells.’