CAR T cell therapy extends beyond cancer

PHILADELPHIA — Engineered immune cells, known as CAR T cells, have shown the world what personalized immunotherapies can do to fight blood cancers. Now researchers have reported 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, MDand Daniel Bakera doctoral candidate in cell and molecular biology at the Perelman School of Medicine at the University of Pennsylvania discuss this development in a commentary published today in Cell.

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

T cells are among the most powerful weapons of the immune system. They can bind to and kill other cells they recognize as valid targets, including virus-infected cells. CAR-T cells are T cells that have been genetically engineered to efficiently kill specifically defined cell types.

CAR T therapies are created from each patient’s own cells – collected from the patient’s blood, then developed and multiplied in the lab before being reinfused into the patient as a ‘living drug’. The first CAR T therapy, Kymriah, was developed by June and his team at Penn Medicine and received approval from the Food & 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 revolutionized the treatment of certain B-cell leukemias, lymphomas and other blood cancers, bringing many patients who otherwise had little hope of long-term remission.

From the beginning of CAR T research, experts believed that T cells could be engineered to fight many conditions other than B cell cancers. Dozens of research teams around the world, including teams from Penn Medicine and biotech spin-offs working to develop effective treatments from personalized cellular therapy constructs developed by Penn, are exploring these potential new applications. June and Baker’s commentary comes in response to the first significant clinical report of success from these efforts: a paper in Naturopathy from German researchers on the use of CAR T therapy against the autoimmune disease lupus (systemic lupus erythematosus).

Researchers say lupus is an obvious choice for CAR T therapy because it is also driven by B cells, and so experimental CAR T therapies against it could use existing anti-B cell designs. B cells are the antibody-producing cells of the immune system, and in lupus, B cells arise that 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 medications within three months of a single, relatively small dose of CAR T therapy, which essentially removed their existing B cells. (Cancer patients then require infusions of purified human antibodies from healthy volunteers to maintain some antibody immunity.) Even more remarkable, all patients 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 the bone marrow.

Baker and June note in their commentary that while the results of the German study need to be confirmed with larger studies and longer-term follow-up, they are promising — they even suggest that lupus could prove to be an easier CAR T target. to be. 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, greatly reducing the problem of immunological side effects.”


Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health Systemwhich together form a $9.9 billion business.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report’s survey of research-oriented medical schools. The school consistently ranks among the top recipients of National Institutes of Health funding in the nation, with a $546 million award in fiscal year 2021.

The University of Pennsylvania Health System patient care facilities include: the University of Pennsylvania Hospital and the Penn Presbyterian Medical Center, recognized by U.S. News & World Report — Chester County Hospital as one of the top “Honor Roll” hospitals in the United States the country; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation’s first hospital, founded in 1751. Other facilities and businesses include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health.

Penn Medicine is powered by a talented and dedicated workforce of more than 52,000 people. The organization also has alliances with top community health systems in both Southeastern Pennsylvania and Southern New Jersey, giving patients more options no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2021, Penn Medicine has provided more than $619 million to our community.

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