The immune system is our unsung hero when it comes to keeping us healthy and disease-free.
Without us realizing it, it mounts defenses 24 hours a day against rogue organisms (from cold and flu viruses to harmful bacteria and even cancer) to prolong our survival as long as possible.
But sometimes (and for reasons that scientists still struggle to understand, despite decades of research) the body’s defense mechanism goes haywire and turns against us, leaving in its wake a trail of incurable, life-changing diseases.
These disorders, called autoimmune disorders, include type 1 diabetes (in which the rogue immune response damages insulin-producing cells in the pancreas); rheumatoid arthritis (which affects joints such as the knees, wrists and fingers and they become painful and swollen); multiple sclerosis (MS, where the immune system destroys the protective layer 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 intestine, causing pain , diarrhea and weight loss). ).
There are at least 80 more, and autoimmune disorders affect around 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 that one 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 by stopping them. ‘reboot’ ‘ the immune system so that it ceases its attacks on healthy tissue.
Current medications simply control symptoms, rather than addressing the underlying disease.
Some experts predict it could be one of the biggest treatment advances in decades.
“CAR T cell therapy was a major breakthrough in the treatment of cancer and could also be a breakthrough for many autoimmune diseases,” says Professor María Leandro, consultant rheumatologist at University College London Hospital (UCLH) and one of the principal investigators of the United Kingdom. in its use for autoimmune diseases.
“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 leukemia in 2018, involves using a blood sample from the patient and collecting T cells in the laboratory.
T cells are a type of defense cell that patrol the bloodstream and destroy any rogue organisms or cells. But it can be difficult for them to distinguish between a cancerous cell and a healthy one. One way around this is to modify T cells by exposing them to a drug that alters their DNA, so that 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 is reproduced in large quantities in the laboratory and a few weeks later injected back into the patient’s body. These drugs, which include Kymriah (also called tisagenlecleucel), have transformed the treatment of blood cancers, with some patients being told they only had months to live and finding themselves in complete remission.
Now UK scientists hope the same treatment could work wonders for autoimmune diseases, for which current drugs simply manage symptoms, rather than addressing the underlying disease.
Instead of attacking cancer cells, in this case the modified T cells would target B cells, another type of immune cell that has its wires crossed and attacks 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 disease 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 taking a lifelong cocktail of powerful medications that can reduce the worst 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 received the treatment as a last resort (when all other medications had failed) and stopped having symptoms within a few months as the therapy “rebooted” her immune system and freed her from the need to take any medication.
Although it is too early to say whether it has worked in UK volunteers, the treatment (which is being tested on 12 patients) is considered by many to be the closest science has yet come to finding a cure for lupus. “Data from the German trials suggest that some patients were still in remission three years after a single CAR T cell treatment,” Professor Leandro told Good Health.
Professor María Leandro believed that since CAR T cell therapy was a breakthrough in cancer treatment, it could also be a breakthrough for many autoimmune diseases.
So if it works for lupus, can it also work for other related diseases? “In theory, yes,” says Professor Leandro. ‘There is a lot of research showing that if we deplete harmful B cells then we can reset the immune system and there are several other diseases where we would expect it to work, including rheumatoid arthritis, type 1 diabetes and multiple sclerosis. ‘
However, he cautions that CAR T-cell therapy cannot reverse damage already caused by an autoimmune disorder. “But we know that in many of these diseases it is possible to detect autoantibodies (destructive proteins activated by harmful B cells) in the blood before the disease appears.”
In the future, that could mean regular testing of people at high risk for the disease, possibly due to family history, he adds.
“Even if we could only postpone the onset of the disease for three to five years with CAR T-cell therapy, that could prevent many of the organ and tissue damage that make these diseases so unpleasant,” says Professor Leandro. .
Early research in mice suggests the therapy could also help fight 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 mistaken attacks of the immune system.
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 deactivate their multiple sclerosis. The trial will last until 2027.
And at least 60 more clinical trials are being organized around the world to investigate the drugs’ effects on a wide range of autoimmune diseases. The results will be eagerly awaited, as some studies suggest that autoimmune diseases are increasing globally, although no one is sure why.
The Diabetes UK charity, for example, says it cannot be down to genes alone, as the increase is happening too quickly for it to be the result of changes to our DNA.
Instead, he is focusing his research on possible triggers, such as a family of viruses called human enteroviruses, which he says appear to be a likely culprit.
They are transmitted through poor hygiene and can cause symptoms ranging from flu-like illnesses to respiratory infections. One theory is that these viruses somehow expose the 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 risks.
Side effects can include something called cytokine release syndrome (in which the immune system reacts to the treatment by causing tachycardia and difficulty breathing), to temporary confusion, slurred speech, and seizures.
“In autoimmune diseases we still don’t know what the long-term effects are in terms of safety and efficacy,” says Dr. Ulrich Blache, an expert in cell and molecular biology at the Fraunhofer Institute for Cell Therapy and Immunology in Germany.
“And the safety bar will certainly be higher for less serious autoimmune diseases. But it is possible that the most common ones (type 1 diabetes, rheumatoid arthritis and multiple sclerosis) could be targeted by CAR T cells in the future.’