CAR-T cell therapy reaches beyond cancer

PHILADELPHIA — Genetically engineered immune cells known as CAR-T cells have shown the world what personalized immunotherapies can do to fight blood cancer. Now researchers have reported very promising early results for CAR-T therapy in a small group of patients with the autoimmune disease lupus. Penn Medicine CAR T pioneer Karl June, MDand Daniel Bakera graduate student in cell and molecular biology at the University of Pennsylvania’s Perelman School of Medicine, discuss this development in a commentary published today in cell.

“We have always known that CART therapies could, in principle, have broad applications, and it is very encouraging to see early evidence that this promise is now being realized,” said June, the Richard W. Vague Professor of 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.

T cells are among the immune system’s most powerful weapons. They can attach 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.

CART therapies are made from each patient’s own cells – collected from the patient’s blood and then developed and multiplied in the laboratory before being infused back 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 Food & Drug Administration approval in 2017. There are now six FDA-approved CAR-T cell therapies in the US for six different types of cancer. The therapies have revolutionized the treatment of certain B-cell leukemias, lymphomas and other blood cancers, and have helped 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 manipulated to fight many diseases other than B cell cancer. Dozens of research teams around the world, including teams from Penn Medicine and biotech spinoffs working to develop effective treatments from personalized cell therapy constructs developed by Penn, are investigating these potential new applications. June and Baker’s comment comes in response to the first significant clinical success story of this effort: an article in naturopathy by 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’s also B cell-powered, so experimental CAR-T therapies against it can use existing anti-B cell designs. B cells are the antibody-producing cells of the immune system, and lupus produces B cells that attack the patient’s own organs and tissues.

In the German study, the patients – five young adults – did not benefit from standard treatments for lupus. Still, all went into remission and were able to stop their lupus medications within three months after a single, relatively small dose of CAR-T therapy, which essentially removed their existing B cells. (Cancer patients subsequently require infusions of purified human antibodies from healthy volunteers to maintain some antibody immunity.) More notably, all patients remained in remission throughout the follow-up period of up to a year, and unlike cancer patients, the lupus patients experienced the return of theirs B cells naturally replenished from blood stem cells in the bone marrow.

Baker and June note in their comment that the results of the German study, while requiring confirmation by larger studies and longer-term follow-up, are very promising – indeed, they suggest that lupus may prove to be an easier CAR-T target as B cell cancer.

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

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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 (established in 1765 as the country’s first medical school) and the University of Pennsylvania Health Systemwhich together form a $9.9 billion company.

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

University of Pennsylvania Health System patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center – recognized by US News & World Report as one of the top honor roll hospitals in the country – Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the country’s first hospital, founded in 1751. Other facilities and companies include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital and Princeton House Behavioral Health.

Penn Medicine is supported by a talented and dedicated workforce of more than 52,000 associates. The organization also has alliances with leading community health care systems in southeastern Pennsylvania and southern New Jersey, creating more options for patients regardless of where they live.

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


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