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'Civil war' in immune system can fight disease
By James Gallagher
Health editor, BBC
9 hours ago
From the section Health
Killer T cell on the attackImage copyright SPL
A T-cell (orange) on the attack
The immune system can be trained to attack itself to reverse a devastating autoimmune disease, in animal studies.
US researchers treated Pemphigus vulgaris in mice by instigating civil war within the immune system, and say the approach could work in people.
Experts said the treatment, published in the journal Science, was creative and successful and they "loved it".
Autoimmune diseases result from the body's defences turning rogue and attacking healthy tissue.
In Pemphigus vulgaris, some B-cells start producing antibodies that attack the glue holding skin cells together.
The result is severe blistering of the skin as well as the lining of the mouth, throat and genitals. It can be fatal.
Skin with pemphigus vulgarisImage copyright SPL
The disease can be treated by using drugs to calm down the whole immune system, but that can leave the patient more vulnerable to infection.
Fight fire with fire
Using the immune system as a weapon to fight disease is already delivering remarkable results in cancer.
One approach is to re-engineer T-cells, which normally specialise in destroying infected cells, to instead attack cancerous cells.
In one study using these modified T-cells, 90% of terminally ill leukaemia patients went into remission.
Researchers at the University of Pennsylvania refined the technique to change the targeting mechanism on T-cells so they attacked only the part of the immune system causing Pemphigus vulgaris.
The experiments on mice showed the characteristic blistering could be prevented, without any impact on the rest of the immune system.
One of the researchers, assistant professor Michael Milone, told the BBC News website: "I think it's an incredibly exciting time; we have the tools to manipulate immunity that we've never had before.
Immunotherapy is changing the treatment of cancer, and we're just at the beginning for autoimmunity.
He believes the approach could also work in similar diseases where there is an obvious antibody causing the problem, such as Myasthenia gravis.
However, other autoimmune diseases such as lupus, type-1 diabetes and multiple sclerosis have very complicated causes that will not be easily treated.
Associate professor Aimee Payne said the therapy could work in patients, but wanted to do more animal research first.
She said: "At this point, we've shown the same data as cancer colleagues did," but added there was concern about doing harm when the disease was not terminal.
Our goal is to cure it in dogs, she said. "If we can do that, then it overcomes the barriers to patients enrolling in trials."
All T-cells have a targeting mechanism that allows them to identify enemies in the body.
Scientists modify the T-cells by fusing a new targeting mechanism on to them to create "chimaeric antigen receptor T-cells" or CAR-T cells.
In Pemphigus vulgaris, the body wrongly produces antibodies to attack a protein called desmoglein, which is normally the glue that holds skin cells together.
The US research team used desmoglein to guide their CAR-T cells to only the white blood cells making the troublesome antibodies.
Prof Danny Altmann, from the British Society of Immunology, told the BBC News website: "I love it, I'm not easily pleased, but CAR-T cell technology has been a wonderful innovation.
"They've done it in a very creative and rather successful way. And this is more than just a mouse paper in Science; it's quite a short hop to being transplantable to a clinical trial."
However, he warned any treatment that resulted was likely to be very expensive.