A Cancer Weapon Turns on the Body's Own Antibody Factories

A Living Drug Borrowed From Oncology

CAR T cell therapy was not invented for autoimmune disease. It was built to hunt cancer. The technique draws immune cells out of a patient’s body, rewires them in a laboratory, and returns them as a targeted strike force. The first federal approval in this class arrived in 2017, when the U.S. Food and Drug Administration cleared engineered T cells for two blood cancers: acute lymphoblastic leukemia and large B cell lymphoma. That origin matters, because it explains the surprise that follows.

The engineered cells carry a molecular homing device called a chimeric antigen receptor, or CAR. T cells normally serve as the body’s security patrol, roaming in search of trouble. The CAR tells them precisely which address to storm. In the cancer setting, that address belonged to malignant B cells, the immune cells that had turned cancerous.

The idea of pointing the same weapon at autoimmune disease once sounded absurd to clinicians. Carl June, the University of Pennsylvania immunologist and oncologist who spearheaded CAR T cell therapy for cancer decades ago, put it plainly: had anyone predicted a CAR T product would win approval for an autoimmune condition, “people would have laughed.” [1] The laughter has since quieted, and the reason sits in a single word — B cells.

The Reset That Rewrites the Instruction Manual

Stiff person syndrome is rare. Population-based figures put the disease at roughly 2 in 100,000 people in the United States, and it typically appears in a person’s 30s or 40s. It is about twice as common in women as in men. The disease is progressive: muscles lock without warning, and falls follow. Celine Dion, who returned to the stage in September after years of battling the condition, has described it as feeling “like somebody’s strangling you.” What links stiff person syndrome to lupus and rheumatoid arthritis is the culprit. In each, a person’s own antibodies attack tissue — blood vessels, cartilage, neurons. The antibodies are not the factory, though. They are the product. The factories are B cells, and that is where the engineered T cells land. Georg Schett, a rheumatologist at Friedrich-Alexander-Universität Erlangen-Nürnberg in Germany, describes the mechanism as complete depletion of B cells in the body, followed by replacement with fresh, unproblematic ones. He calls it an “immune reset.” The old instruction manual is torn up; a clean copy is printed.

The evidence that this could work in autoimmune disease came in stages. In 2021, Schett’s team published the first major report of a successful treatment: a 20-year-old woman with severe lupus. Within five weeks, signs of her disease began to vanish. Results of that kind were “unheard of,” says rheumatologist Maximilian Konig of Johns Hopkins Medicine in Baltimore. [1] Lupus had defeated most drugs tested against it for decades. More than five years later, the woman’s lupus has not returned. “We consider this patient cured,” Schett says. [1] The following year, Schett’s team reported similar outcomes in five more lupus patients, all of whom went into remission. June calls such striking results “rare, very rare.” That was the tipping point, June says. Research then spread worldwide, with trials now testing the approach in nearly a dozen autoimmune diseases tied to harmful B cells.

The stiff person syndrome trial belongs to Kyverna, a California-based company. Its product, miv-cel, was given to Lynn Montgomery-Haga, the first person in the United States to receive it for the disease. Before treatment, the 49-year-old struggled to walk 25 feet and often reached for walls. Her neurologist, Amanda Piquet of the University of Colorado Anschutz, described a “very stiff, hesitant gait.” Montgomery-Haga had lost her accounting job and her ability to drive. Dropping the soap in the shower cost her ten minutes.

A Cancer Weapon Turns on the Body's Own Antibody Factories (Image 1) — AI-generated image

Four months after the infusion, Piquet’s team repeated the walking test. This time the gait was smooth and the arms hung down rather than hovering for balance. Eight of 12 people who had used a walking aid in the initial test did not need one at follow-up, Piquet reported at the American Academy of Neurology meeting in April. At one year, Kyverna reported that patients maintained their mobility gains, with a third completing the 25-foot walk about as fast as a healthy adult. Nearly all no longer rely on immunosuppressive drugs. Montgomery-Haga, who once rated her condition a zero out of ten, now places herself near seven. “I think I’m still improving,” she says.

Where Neurology Meets the Blood-Brain Barrier

The next question is not whether the reset works, but where else it can reach. Kyverna is also running trials in generalized myasthenia gravis and progressive multiple sclerosis. The appeal for neurological disease is anatomical: engineered cells may slip past the blood-brain barrier, the tightly guarded border that keeps most drugs out of the central nervous system.. Rebecca Farber, a neurologist at Columbia University, notes that this access could let the cells reach pockets of smoldering inflammation that other medicines cannot touch.

The caution is equally anatomical. In multiple sclerosis, antibodies attack the protective sheaths around nerve cells, producing numbness, brain fog and difficulty walking. Farber does not expect the therapy to repair damage already done. “We’re not expecting it to repair the nervous system,” she says. Freezing the disease’s progress, however, is a different and plausible aim. Patients are already asking her team about future treatments.

Safety remains the open file. The preparation is punishing: low-dose chemotherapy clears space for the engineered cells but can bring hair thinning, nausea, vomiting and diarrhea. The treatment destroys most B cells, not only the harmful ones, and in Kyverna’s trial 15 percent of participants had severely low white blood cell counts afterward — expected, Piquet says, and easily treated. Other programs have fared worse. In August, Novartis paused trials of its therapy, rap-cel, across a spectrum of autoimmune diseases after three patients died. Bristol Myers Squibb also paused similar studies after some patients experienced neurological complications, according to the Wall Street Journal. “It’s a tragedy,” Konig says, calling the outcomes an important wake-up call.

Konig’s caveat is that one troubled product does not condemn the class. Designs and manufacturing processes differ, and scientists cannot always predict which will prove toxic. Kyverna says miv-cel has been consistently well-tolerated in more than 100 patients treated. June adds a longer horizon: there may be long-term complications in autoimmune patients that never appeared in cancer patients. Marc Scherlinger, a rheumatologist at Strasbourg University Hospital in France, urges restraint. “It’s very important not to oversell it,” he says.

Tara Zier, a former dentist in Maryland who founded The Stiff Person Syndrome Research Foundation, illustrates why some patients wait. She saw 13 specialists and visited the emergency room nine times before her diagnosis. She has tapered off all but a low dose of Valium, and describes the trade-off as pain. A single mother of two, she says a rare side effect could disrupt a life she has learned to manage. The therapy’s future now rests with regulators: Kyverna is submitting miv-cel for approval, seeking priority review, and hopes for availability in 2027. If stiff person syndrome becomes the first autoimmune disease with an approved CAR T therapy, myasthenia gravis could be the second, says Kyverna CEO Warner Biddle. The same product also appeared to improve symptoms in six patients with severe rheumatoid arthritis, researchers reported in Nature Medicine in August.

Sources

Sciencenews — Quote source (original article)

A Cancer Weapon Turns on the Body's Own Antibody Factories (Image 2) — AI-generated image