Illustration of a CAR T-cell with an implanted gene strain, resulting from the genetic modification process required for it to fight rogue cells in the body
CHRISTOPH BURGSTEDT/SCIENCE PHOTO LIBRARY
A woman who had three different autoimmune conditions has not required treatments for almost a year after her immune cells were genetically modified and used to kill off the rogue cells attacking her body. “She was deathly sick and bedridden at the time we met her, and we treated her, and seven days later, she got out of bed,” says Fabian Müller at the University Hospital of Erlangen in Germany. Within months she appeared to be fully recovered. “I just saw her yesterday. She’s perfectly fine,” says Müller, speaking 11 months after the treatment.
This woman is one of a growing number of people with autoimmune conditions who have been successfully treated this way, and the first to have three different ones treated simultaneously. “The really crazy thing is that you have three autoimmune diseases, and all three of them, by chance, you can tackle with one treatment,” says Müller.
In response to, say, a viral infection, our bodies generate lots of new immune cells with random mutations. These mutant cells then undergo a screening process to select those that make antibodies that bind to the virus, and to weed out any making antibodies that attack our own bodies. But sometimes, self-targeting immune cells slip through this selection process and, once they do, they can persist for a lifetime.
In the woman’s case, this happened when she became pregnant more than a decade ago. Her body started producing antibodies that bound to her red blood cells, which carry oxygen from the lungs to the rest of the body, resulting in their destruction. This potentially deadly condition is called autoimmune haemolytic anaemia.
Her immune system also started producing antibodies that targeted her platelets, cell fragments that help blood to clot – a condition called immune thrombocytopenia. Thirdly, it began making antibodies against certain proteins that help prevent blood clots, meaning she simultaneously had a greater risk of the opposite problem: of dangerous blood clots forming, known as antiphospholipid syndrome.
The woman had been treated with a number of immune-suppressing drugs but none worked well. She required regular blood transfusions to survive, along with blood-thinning medications to prevent clots.
She was eventually referred to Müller, whose team was the first to treat autoimmune conditions with CAR T-cells in 2022. Before this, CAR T-cells had only been used for treating cancer.
CAR T-cells are T-cells – immune cells that usually kill infected or cancerous cells – that are taken from the person undergoing treatment. In the lab, they are genetically engineered to make them attack a specific target and then infused back into that person.
To treat the woman, Müller’s team made CAR T-cells that target the immune cells that produce antibodies. When the modified cells were infused into her, they killed off her antibody-producing cells.
This didn’t completely erase her immune system – she still had unmodified T-cells, and also her oldest antibody-producing cells against childhood infections and vaccinations. “They sit in the bone, they’re unaffected,” says Müller.
In fact, her immune system recognised the CAR T-cells as foreign and killed them all off within months, allowing new antibody-producing cells to form. This means her immune system has returned to normal, but without a bunch of antibody-forming cells, including those that were causing her illness.
The CAR-T approach has shown promise for a wide range of autoimmune conditions, including lupus, multiple sclerosis, colitis and severe asthma. When CAR T-cells are used to treat cancers they often trigger serious side effects, but this is not being seen with autoimmune conditions. These side effects might be a result of killing huge numbers of cancerous cells, says Müller. With autoimmune conditions, far fewer cells need to be killed.
The woman does have some minor lingering effects, but the team thinks these are a result of her previous drug therapies, rather than the CAR-T treatment. “For a therapy that’s very powerful to have very few side effects in this particular case, and then to result in resolution of the underlying condition, is pretty remarkable,” says Reuben Benjamin at King’s College London. “This is a fantastic result.”
So far, most people treated for autoimmune conditions via CAR T-cell therapy have remained disease-free, Benjamin says, but there have some cases where the self-targeting cells have reappeared and another CAR-T treatment was required.
“Longer follow-up is needed before anyone can speak confidently about cure,” says Jun Shi at the Chinese Academy of Medical Sciences in Tianjin, whose team has used a CAR T-cell therapy on 15 people with autoimmune haemolytic anaemia as part of an ongoing trial.
CAR-T treatments are extremely expensively because of their personalised nature – for cancers, the cost ranges from $200,000 to $600,000 – but Müller points out that the ongoing costs of treating autoimmune conditions can add up to even more, plus the treatments are so effective that people are often able to return to work. “It costs a lot to start with, but you save a lot of money in the long run,” he says.
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