Single CAR T Injection Eases Multiple Sclerosis Symptoms in Small Trial

When the body goes to war on itself, it wreaks havoc.

The immune system is one of our most powerful defenses, protecting us from infections, cancer, and other threats. But it’s a double-edged sword. Sometimes all that firepower is turned against healthy tissue. The resulting autoimmune diseases can be devastating. Take multiple sclerosis, an insidious disease that gradually eats away at the insulating coating around delicate nerve fibers, scrambling the electrical signals that control our bodies. The disease often strikes in young or middle adulthood, and there’s no cure.

Now a new clinical trial turns the immune system’s arsenal against the cells driving the autoimmune attack. Called CAR T cell therapy, the approach has already had success tackling previously untreatable blood cancers. Normally, CAR T cells are isolated and genetically engineered in specialized facilities. But in the new trial, with a single injection, researchers delivered a virus carrying genetic instructions to reprogram T cells in the body.

In 16 patients with autoimmune disorders affecting the nervous system, the treatment had few severe side effects. It also seemed to hit a kind of immune reset button. Follow-up tests suggested that the treatment restored parts of patients’ immune systems to normal, and there were no signs the friendly fire had returned. Across three different diseases, symptoms and molecular markers improved for over six months.

“These findings provide proof-of-concept that in vivo [in the body] CAR T-cell generation is associated with manageable side effects and may be effective for treating refractory neurologic autoimmune disorders,” wrote the team.

The study was small, and there was no control group. But it brings the dream of a simpler, cheaper, and more affordable CAR T therapy a step closer. This could, in turn, give more people access to the drug.

“It’s a clear go signal for a further study,” Georg Schett at University Hospital Erlangen, who wasn’t involved in the work, told Science.

Outside In

Once a niche treatment for blood cancer, CAR T therapy has quickly expanded, with over 1,500 clinical trials registered worldwide. Hope is high CAR T can battle solid tumors, which account for more than 85 percent of cancer cases, and even stop them from spreading. It’s also being repurposed to take on a range of autoimmune disorders, such as lupus, with promising early results.

But there’s a catch. Making CAR T cells is a logistical nightmare.

Traditionally, doctors must harvest a patient’s T cells and genetically edit them outside the body to produce protein “bloodhounds” called chimeric antigen receptors, or CARs. These proteins sit on each engineered cell’s surface and help it recognize a specific target. Once CAR T cells are infused back into the patient, they hunt down and attack disease-causing cells involved in some cancers and autoimmune disorders.

The whole production can take weeks—precious time some patients don’t have. A price tag in the hundreds of thousands of dollars keeps the therapy out of reach for many. And the need for toxic chemotherapy, which clears out existing immune cells to make room for CAR Ts, leaves people vulnerable to infection and adds another burden to an already grueling treatment.

So, researchers have pursued shortcuts. One idea is to skip the individualized manufacturing step and use healthy donated T cells to save time and cost. But this can trigger immune rejection, where the body wipes out the “invaders,” or spark dangerous reactions against the patient’s own tissues.

These risks aren’t just speculation. The pharmaceutical giant Novartis recently halted eight CAR T trials for autoimmune disorders after three participants died from a severe inflammatory complication. While the tragedy is still under investigation, one possible cause is that the engineered cells expanded and activated too rapidly.

In another popular alternative, researchers alter a patient’s own T cells inside their body. Dubbed in vivo, this method delivers a synthetic gene encoding the CAR protein to T cells, turning them into super-soldiers on the spot. In theory, the same genetic formulation could work for many people, making CAR T therapy more like a drug and slashing time and cost. The approach also spares patients from chemotherapy and could be safer.

But it’s tricky business. Transforming isolated T cells outside the body limits the added gene to only that population. Inside the body, scientists have far less control over where the genetic cargo goes. A delivery system meant only for T cells could reach other cell types or inadvertently integrate into the genome, spurring mutations that contribute to cancer. Still, some creative workarounds that boost safety and efficacy have already shown promise in mice.