CAR T Cell Therapy reaches beyond cancer

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Chimeric antigen receptor cells (CAR T), or engineered immune cells, have revealed the ability of personalized immunotherapies to fight blood cancers. Now, researchers have reported highly promising early results for CAR T therapy in a small group of patients with the autoimmune disease lupus. Penn Medicine CAR T pioneer Carl June, MD, and Daniel Baker, a doctoral student in Cell and Molecular Biology in the Perelman School of Medicine at the University of Pennsylvania, discuss this progress in a commentary published today in Cell.

"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," said 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.

Read: Immunotherapy treatment "cures" 2 cancer patients

T cells are among the immune system's most powerful weapons. They can bind to and kill the cells they see as valid targets, including cells infected by viruses. CAR T cells are T cells that have been redirected to effectively kill specifically defined cell types, through genetic engineering.

How are CAR T therapies created?

The cells of each patient are what make CAR T therapies; they are collected from the patient's blood and engineered and multiplied in a lab before they are re-infused into the patient as a "living drug."

The first CAR T therapy, Kymriah, was developed by June and his team at Penn Medicine. It was approved by the Food and Drug Administration in 2017. There are now six FDA-approved CAR T cell therapies in the United States for six different cancers. The therapies have created a revolution in the treatment of certain B cell leukemia, lymphoma, and other blood cancers. Many patients who had little hope have now been put into long-term remission.

Since the beginning of the research, experts believed that T cells could be engineered to fight many conditions other than B cell cancers. These potential new applications are being examined by dozens of research teams around the globe.

The commentary from Baker and June comes in response to the first significant clinical report about the success resulting from these efforts: a paper in Nature Medicine by German researchers on the CAR T therapy used to fight the autoimmune disease lupus (systemic lupus erythematosus).

Lupus, according to researchers, is an obvious choice for CAR T therapy because it, too, is driven by B cells. Thus, experimental CAR T therapies can employ existing anti-B-cell designs. B cells are the immune system's antibody-producing cells, and, in lupus, B cells arise and attack the patient's own organs and tissues.

In the German study, the patients, five young adults, did not benefit from standard lupus treatments. Yet, they 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.

What was even more noticeable is that all the patients remained in remission during the follow-up period of up to a year, and unlike cancer patients, the lupus patients' B cells came back. They are naturally replenished from blood stem cells in the bone marrow.

June and Baker noted in their commentary that, although the German study's results should be confirmed with bigger studies and longer-term follow-up, they are significantly promising. 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."