One shot just wiped out three deadly autoimmune diseases

The 47-year-old woman was at the end of her rope.

In 2014, she was diagnosed with a rare form of anemia. Her body’s B cells, which normally produce antibodies to fight infections, stopped, endlessly attacking red blood cells that carry oxygen. Two other autoimmune diseases soon followed, one crippling her body’s ability to stop bleeding and the other increasing her risk of blood clots.

She tried nine treatments. Nothing helped. Her life was centered on blood transfusions, up to three times daily, to keep symptoms at bay. But the constant fatigue made every day a struggle. Her life was threatened by fatal bleeding or blood clots.

Of the options, her care team tried an experimental treatment called CAR T-cell therapy. They made a “living drug” from the patient’s own T cells, editing the cells’ DNA so that they could seek out and destroy a specific biological enemy. Although CAR T is best known as a treatment for blood cancers, it also shows great promise in autoimmune diseases. Trying to take on three conditions at once raised the bar, but it worked.

A single infusion of the engineered cells quickly killed the misbehaving B cells. The woman was able to stop the blood transfusion within a week, and her red blood cell count was almost normal after about a month. Her strength returned, and after 11 months of follow-up, she was off medication and could enjoy life again.

“It was a completely uncontrolled disease. And now it has refused any therapy. That tells you that, at least for the time being, we did something very right,” study author Fabian Müller of the University Hospital Erlangen in Germany told Nature.

Runaway train

The body’s B cells are powerful defenders. They watch for infections or cancer, produce antibodies to eliminate threats, and rally other immune cells to join the fight.

But sometimes B-cells break down. Genetic mutations can lead to blood cancer. Some B cells have difficulty making antibodies, making them powerless to fight infection. And in autoimmune diseases, cells mistakenly attack and damage healthy tissue — a kind of immune friendly fire — that can damage organs if left untreated.

In the woman’s case, faulty B cells mercilessly attacked red blood cells, robbing them of their ability to carry oxygen. They also destroyed platelets, tiny disk-like fragments in the blood that stop bleeding. The cells also attacked a protein that helps prevent blood clots.

That triple hit ‘can kill you real quick’ said CAR T pioneer Carl June of the University of Pennsylvania, who was not involved in the study.

Steroids to suppress the immune system did not work. Neither B-cell-inhibiting antibodies nor other classic autoimmune drugs did either. After trying nine treatments and exhausting options, the team suggested CAR T-cell therapy as a last resort.

CAR T drugs are typically made from a patient’s own T cells, genetically engineered to hunt, capture and destroy targets. Researchers originally developed CAR T to treat blood cancers, but efforts are underway to expand its use against solid rivers. In other studiesscientists have made these soldiers who fight cancer directly inside the body reduce cost and time. Because CAR T cells can divide and replenish their numbers, a single dose may be enough for more than a decade.

The treatment is basically plug and play. The surfaces of all cells are dotted with protein beacons. Tumors have a unique protein signature. B cells also have one – a protein called CD19. Scientists already had early success treating autoimmune diseases by engineering CAR T cells that selectively hunt down and destroy B cells.

A small CAR T trial in 2014 restored movement in patients with systemic sclerosis, a disease that causes tissue stiffness. Earlier this year, Mueller was in charge clinical trial testing Zorpo-cel, T cells engineered to seek out CD19, in various autoimmune diseases with promising results. Six months after treatment, all patients stopped using steroids and other treatments.

“For the first time in severe autoimmune disease, you really have a treatment-free period,” Muller told Medscape at that time. “It’s a really new perspective that’s never been seen before.”

One for all

Battling three autoimmune diseases at the same time was uncharted territory. Too many CAR T cells can trigger a deadly immune response that can even threaten the brain.

The team turned to Zorpo-cel. In the lab, they isolated the woman’s T cells and edited them to produce protein “hooks” that targeted CD19. The patient then underwent standard chemotherapy to destroy most of her immune system. Obviously, this step is very hard on the body, but it is necessary to remove the immune cells that will block the CAR T.

A week after the infusion, the woman’s red blood cells recovered, ending the need for a blood transfusion. After a month, most of her disease-related blood tests had improved, and she “experienced a rapid and significant increase in physical strength and was able to perform normal daily activities,” the team wrote.

Now, a year later, she no longer needs the “two handfuls of pills” she used to take to manage the condition. Her liver struggled at several points during the ordeal, but she avoided severe immune reactions and other serious side effects. It is unclear whether the liver problems were due to the CAR T or long-term damage from earlier treatments.

Fighting three autoimmune diseases with CAR T is unprecedented. But there are limitations. This is a single-case study, and the researchers will need to follow the patient’s health over time. Additionally, CAR T cells can decline and allow target cells to return. At the end of the study, the team found signs of newly formed B cells. However, they were “naïve” in the sense that they had not yet learned how to affect normal tissues – and they may never learn.

Hundreds of CAR T clinical trials targeting autoimmune diseases are in the works. Several commercial companies joined the race. “I think within a year or two the approvals will be in place in the US,” June said.