As a rheumatologist at Columbia University Medical Center, I routinely care for patients with autoimmune diseases. I’m grateful that, in recent years, biologics such as Humira, Enbrel, and Xeljanz—synthesized molecules designed to target specific immune pathways—have been effective against conditions like rheumatoid arthritis, psoriasis, and inflammatory bowel disease. But biologics sometimes don’t work well for lupus, likely because the disease causes such a wide range of symptoms and affects multiple immune pathways. Survival rates for lupus climbed between the nineteen-forties and the nineties, but they have largely plateaued. Women develop the disease in much higher numbers than men; severe cases disproportionately affect Black and Hispanic patients. A person diagnosed before age forty is twelve times as likely to die prematurely as someone without the condition. “I go to fewer funerals these days,” Anca Askanase, a colleague who directs the Columbia Lupus Center, told me. “But there are still too many.”
T cells are the foot soldiers of the immune system, capable of identifying threats and mounting attacks. In the eighties, Michel Sadelain, a French-born graduate student in Canada, wondered if T cells could be instructed to kill cancer cells. The answer was yes, but with limitations: T cells rely on a molecule called HLA to recognize targets, and cancers can avoid detection by limiting their expression of HLA.
In the late eighties, an Israeli scientist named Zelig Eshhar successfully fused a T-cell receptor with an antibody, which could recognize cancer cells without relying on HLA. Eshhar’s “T bodies” could bind to tumors, but they were weak and short-lived. Sadelain addressed this problem by engineering a molecule that he called a chimeric antigen receptor (CAR), which activated the T cell’s internal engine, stimulating it to survive and kill repeatedly. He also programmed his CAR-T cells to target CD19, a marker found on nearly all B cells, including those involved in many blood cancers.
In 2010, Bill Ludwig, a sixty-five-year-old with a terminal form of leukemia, became one of the first patients treated with CAR-T cells. The infusion initially left him critically ill: like Reid, he experienced cytokine storm. But, after the storm passed, he was cancer-free until he died, in 2021, of COVID-19 pneumonia. The F.D.A. went on to approve seven CAR-T products, and cellular therapies became a transformative option for tens of thousands of cases of treatment-resistant blood cancers. (They are not without side effects: in November, 2023, the F.D.A. announced that nineteen recipients of CAR-T cancer therapies had reported new T-cell cancers, and the agency now recommends that patients be monitored for life.)
CAR-T’s lupus breakthrough came in 2021, when Georg Schett, a physician at the University of Erlangen-Nürnberg, in Germany, met a young woman with life-threatening lupus who had exhausted all available treatments. Schett had little to offer except an experimental CAR-T therapy, which had appeared to work in mouse models of lupus. The patient agreed, and within weeks of her infusion she was in full remission—a recovery that Schett had never seen before. “It was our eureka moment,” he told me.
Schett and his team treated more lupus patients. Romy Kandera, who received an infusion at eighteen years old, had been a talented pianist until lupus caused swelling in her fingers. While learning a Chopin piece that spanned several octaves, she realized that she could not reach the notes. “Playing music made me special, and I felt like with lupus I was losing that,” she told me. Yet since her CAR-T therapy, in January, 2022, she has been in a drug-free remission. She is now a student in Düsseldorf, and in her free time she has returned to playing piano.
CAR-T treatments for lupus may not work in every patient, George Tsokos, the chief of rheumatology at Beth Israel Deaconess Medical Center, told me. “No two lupus patients are alike,” he said. “Everybody has their own disease.” He also cautioned that “the experience from treating cancer patients cannot just be transferred over to patients with autoimmune disease.” Our immune systems remain complex and mysterious; they are defined not only by our immune cells but also by our genes and our environments, which are unchanged by CAR-T therapy.
