This story is part 3 in a four-part series about cell therapy created by the Fierce Biotech team. Part 1 is available here, part 2 is here and the final installment is here. Gabrielle Masson, Helen Floersh, James Waldron and Max Bayer contributed reporting to this series.
The patient had cycled through every possible treatment for systemic lupus erythematosus, yet at just 20 years old still suffered from some of the autoimmune condition’s worst consequences—endocarditis, pleurisy, arthritis and urine protein levels 40 times higher than normal, a sign of possible kidney failure. In a last-ditch attempt to salvage her poor prognosis, her care team at University Hospital Erlangen in Germany decided to try an experimental CD19 chimeric antigen receptor T (CAR-T) cell therapy against the autoreactive B cells causing her disease.
“This decision was not an easy one—we feared that she would suffer from a severe cytokine storm [a life-threatening immune reaction],” Georg Schett, M.D., one of the doctors who treated the patient, recalled during a lecture in early April 2024 at the German National Academy of Sciences Leopoldina.
But that didn’t happen. Instead, after just one treatment, “she had a remarkable resolution of lupus,” Schett said. Her protein levels normalized after 30 days. Her anti-dsDNA antibodies—a lupus biomarker—fell quickly and eventually disappeared entirely. So did the autoreactive B cells that had been attacking her own organs.
“That was the first initiation that this might really work,” Schett recalled. Three years later, the patient is still healthy, living a normal life without treatment or signs of autoimmunity. Her B cells have even returned—but this time, they aren’t autoreactive.
This patient was the first of 15 whose CAR-T treatment for lupus, systemic sclerosis and idiopathic inflammatory myositis are documented in a series of papers published by Schett and his colleagues at University Hospital Erlangen. At the time of Schett's presentation, nearly all of those subjects continued to have no signs of disease and remained treatment-free. The results have sparked a frenzy of interest in CAR-T therapy for autoimmune disease, with companies like CRISPR Tx, Kyverna, Novartis and others investing in the approach.
Even Regeneron, an immunology powerhouse as one-half of the team behind the monoclonal antibody Dupixent, took notice.
“There’s a lot of excitement about the recent data using classically oncology targets to drive very transformative outcomes for patients with autoimmune disease like lupus and others,” Philip Gregory, head of Regeneron Cell Medicines, told Fierce Biotech at the American Society for Gene and Cell Therapy meeting in early May.
While preclinical studies hinted at CAR-T’s potential in autoimmune disease, it was academic patient studies that came out of Germany that “ignited the excitement,” Sami Corwin, Ph.D., a healthcare analyst at William Blair, told Fierce Biotech. “[They] kind of showed that for the first time, you might be able to induce an immune reset in severe autoimmune patients that could lead to a durable drug-free remission.”
CAR-T cell therapy has been the darling of the oncology world for more than a decade, where it’s had most success against blood cancers. That includes acute B cell lymphoblastic leukemia and B cell lymphoma, malignancies that affect the same type of immune cells that are autoreactive in lupus and other autoimmune diseases.
For CAR-T applications, that overlap makes for a rational switch between oncology and immunology, Cartesian Chief Medical Officer Miloš Miljković, M.D., told Fierce Biotech. Cartesian is currently conducting clinical trials on Descartes-8, an autologous BCMA-directed, mRNA-engineered CAR-T therapy to treat the autoimmune disease myasthenia gravis. That condition has a similar disease mechanism to lupus but affects the neuromuscular system specifically rather than the whole body.
“It wasn't surprising because [with CAR-T therapy for cancer] you're targeting B cells, you're targeting plasma cells. Both are involved in autoimmune disease heavily,” Miljković said. “So it was a straightforward connection to make.”
As clinical trials for CAR-T therapy in autoimmune conditions get underway, there are reassuring signs from the University Hospital Erlangen’s CAR-T research that the same protocols for cancer can be adopted for autoimmune disease. The patients in the institution’s study received the same dose of CAR-T cells used in a phase 1 trial on B cell lymphoma. They had no issues with T cell transduction or cell expansion. And side effects were limited to fevers; none of the patients experienced cytokine release syndrome or immune effector cell-associated neurotoxic syndrome, two serious concerns with CAR-T therapies in oncology.
“We think [the absence of severe side effects] is because the target engagement with cancer is much higher—with a higher burden of B cells in the body—than in autoimmunity, so the level of CAR-T cell engagement at once is much lower,” Schett explained. “Therefore, we have less cytokine release.”
Still, despite their impact on the industry and positive results so far, the early studies were small and focused on only three autoimmune conditions. The approach’s future effectiveness will likely hinge on disease and patient selection, Schett said. The disease should be truly B-cell mediated, and patients can’t have so much organ damage that it precludes improvement. Furthermore, results could vary according to target selection, lymphodepletion and whether the patient is on other kinds of drugs, particularly those that affect T cells.
Researchers should also figure out how they plan to treat relapses. The center has seen one so far—“a recent development,” according to Schett. In that case, they decided to do a “re-exposure” with existing CAR-T cells. Other options might include glucocorticoids if the returning disease is mild, he said.
Challenges aside, it may be only a matter of time before biotechs pivot to yet another application for CAR-T therapy. The researchers at University Hospital Erlangen are assessing the treatment in HIV, cardiac fibrosis, hepatitis B and even cell senescence, a hallmark of aging.
Editor's note: This story is part of a series on cell therapy. The fourth and final part will be published May 31.