CAR T Shows Promise in Treating Lupus

Researchers in Germany report good preliminary results using personalized cancer immunotherapy CAR T to treat autoimmune disease lupus—validating hopes that the breakthrough treatment could be applied beyond cancer.

CAR T therapies leverage a patient’s own T cells, which are among the immune system’s most powerful weapons. It works by collecting T cells from a patient’s blood, engineering and multiplying them, and re-infusing them into the patient to act a living drug. The first CAR T therapy, Kymriah, was developed by University of Pennsylvania School of Medicine pioneer Carl June, MD and his team at Penn Medicine and received Food & Drug Administration approval in 2017. There are now six FDA-approved CAR T cell therapies in the United States, for six different cancers. The therapies have revolutionized the treatment of certain B cell leukemias, lymphomas, and other blood cancers, putting many patients who otherwise had little hope into long-term remission.

From the start of CAR T research, experts believed the therapy could be used to fight many conditions other than B cell cancers. Dozens of research teams around the world, including teams at Penn Medicine and biotech spinoffs who are working to develop effective treatments from Penn-developed personalized cellular therapy constructs, are examining these potential new applications. Recently, a paper in Nature Medicine from German researchers reported the first good clinical results using CAR T therapy against systemic lupus erythematosus. In a subsequent commentary in the journal Cell, June and Daniel Baker, a doctoral student in Cell and Molecular Biology at the Perelman School of Medicine at the University of Pennsylvania, lauded the results of the small study.  

“We’ve always known that in principle, CAR T therapies could have broad applications, and it’s very encouraging to see early evidence that this promise is now being realized,” says June, who is the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine at Penn Medicine and director of the Center for Cellular Immunotherapies at Penn’s Abramson Cancer Center.

In the German study, the patients—five young adults—did not benefit from standard lupus treatments but all went into remission and were able to stop taking their lupus drugs within three months of a single, relatively small dose of CAR T therapy, which essentially removed their existing B cells. When treating cancer, patients subsequently require infusions of purified human antibodies from healthy volunteers to maintain some antibody immunity. Even more remarkably, all the patients in the German study remained in remission during the follow-up period of up to a year, and, unlike cancer patients, the lupus patients experienced the return of their B cells, which are naturally replenished from blood stem cells in bone marrow.

Researchers say lupus is an obvious choice for CAR T therapy because it too is driven by B cells, and thus experimental CAR T therapies against it can employ existing anti-B-cell designs. B cells are the immune system’s antibody-producing cells, and, in lupus, B cells arise that attack the patient’s own organs and tissues.

Baker and June note in their commentary that, although the German study’s results need to be confirmed with larger studies and longer-term follow-up, they are highly promising—indeed, they suggest that lupus could turn out to be an easier CAR T target than B-cell cancers.

“Disease-driving B cells are much less numerous in lupus,” Baker said. “Thus, effective CAR T treatment of this autoimmune disease may require a much lower dose that greatly reduces the problem of immunological side-effects.”