New Scientist
CAR T-cells, once built to fight blood cancer, are now showing stunning promise against autoimmune diseases.
We may finally have a remedy for autoimmune conditions
Author: Michael Le Page
OUR immune systems never stop targeting cells they regard as a threat, so it’s bad news when rogue immune cells turn on us, as they do in autoimmune conditions. Existing treatments suppress, but don’t stop, these attacks. But an approach that addresses the cause of these disorders by killing off the rogue cells is proving wildly successful.
There are dozens of clinical trials under way, and the first treatments could be approved as early as next year, says Reuben Benjamin at King’s College London.
The key is genetically engineered cells known as CAR T-cells. These are made from the T-cells your immune system usually employs to kill off invasive bacteria or virus-infected cells. The T-cells are extracted from a person, programmed to attack a specific kind of cell and then returned to that individual.
CAR T-cells were developed for treating cancers, where they can help people when other treatments have failed. But they only work for blood cancers, not solid tumours. And they can trigger serious side effects, such as brain inflammation.
Using CAR T-cells for autoimmune conditions is working better than anyone dreamed five years ago
Cancers are caused by mutant cells that keep growing and dividing when they should stop. Autoimmune conditions are also caused by rogue cells, in this case ones that attack a certain organ or cell type. For instance, type 1 diabetes is caused by an immune attack on the cells in the pancreas that produce insulin.
After the body generates new immune cells in response to an infection, they undergo a screening process that should weed out any that mistakenly attack our bodies. But sometimes this process fails, and these rogue cells can then persist for the rest of our lives.
A study last month confirmed an idea proposed in the 1950s, that these rogue cells have mutations in key genes involved in screening. As a result, they don’t kill themselves off when they should – meaning autoimmune conditions are more similar to cancers than we thought.
However, it wasn’t obvious that CAR T-cell treatments would work well for autoimmune conditions. One issue is that rogue immune cells don’t stand out, so you have to kill off most antibody-producing cells, not just the rogue ones.
In people treated for cancers, CAR T-cells can persist for many years, which is useful. But it seemed that using them to treat autoimmune conditions would leave a hole in people’s immune defences.
Even with the risks, around five years ago, Fabian Müller’s team at the University Hospital of Erlangen in Germany decided to treat people with lupus using CAR T-cells.
“The first few patients were so sick that they would have died without the treatment,” says Müller. To the team’s astonishment, the CAR T-cells did their job and then disappeared after a few months.
Müller thinks CAR T-cells persist in people treated for cancer because their immune systems are weakened, whereas in people with autoimmune conditions, the immune system is intact and recognises the CAR T-cells as foreign.
Then there are those potentially deadly side effects – they’re just not happening in people treated for autoimmune conditions. “That’s really miraculous,” says Müller.
He thinks there are three explanations for the surprising findings. Firstly, CAR T-cells are killing huge numbers of cells in people with advanced cancers, but have far fewer cells to target in those with autoimmune conditions. Secondly, the quality of CAR T-cells from people with autoimmune disorders is higher, probably because they haven’t had treatments targeting cancerous immune cells. Finally, the immune systems of people with cancer may be releasing lots of alarm signals, causing the CAR T-cells to overreact.
Worldwide, it’s likely that several hundred people have been treated for autoimmune diseases using CAR T-cells, and while trial results aren’t yet in, case reports suggest it is remarkably effective for treating conditions such as lupus, myasthenia gravis and ulcerative colitis. Doctors are cautious about calling it a cure, but where the CAR T-cells kill off all the rogue cells, these treatments very well could be that.
However, the damage caused by self-targeting immune cells isn’t always reversible. And not all rogue immune cells are easy to target, so it remains to be seen in how many autoimmune conditions this approach will work.
But so far, using CAR T-cells for autoimmune conditions is working better than anyone dreamed five years ago. That’s fantastic news for the around 1 in 10 of us affected by them.
Credits: TCA, LLC.