CAR T therapy extends its scope well beyond oncology



Engineered immune cells, known as CAR T cellsshowed the world what personalized immunotherapies can do to fight blood cancers. Now, researchers report very promising early results for CAR T therapy in a small group of patients with the autoimmune disease lupus. Penn Medicine CAR T pioneer Carl John, MD, and Daniel Becker, PhD student 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.

said John, MD, the Richard W. Fagg Professor of Immunotherapy in the Department of Pathology and Laboratory Medicine at Penn Medicine and director of the Center for Cellular Immunotherapy at Abramson Cancer Center in Pennsylvania.

T cells are one of the immune system’s most powerful weapons. They can bind to other cells they recognize as valid targets, including virus-infected cells, and kill them. CAR T cells are T cells that have been redirected, through genetic engineering, to effectively kill specific cell types.

CAR T therapies are created from each patient’s cells – ; It is collected from a patient’s blood, then engineered and compounded in a laboratory before being reinjected into the patient as a “live drug”. The first CAR T therapy, Kymriah, was developed by June and his team at Penn Medicine, and received FDA approval in 2017. There are now six FDA-approved CAR T cell therapies in the United States, for six different types of cancer. The therapies have revolutionized the treatment of some B-cell leukemias, lymphomas, and other types of blood cancers, putting many patients who had little hope of long-term recovery at bay.

Since the beginning of CAR T research, experts have believed that T cells could be engineered to fight many conditions other than B cell cancers. Dozens of research teams around the world, including those at Penn Medicine and biotechnology subsidiaries that are developing effective therapies from the personalized cell therapy formulations developed by Penn, are examining these potential new applications. The comment from June and Baker comes in response to the first clinical report critical to success from these efforts: a paper in Nature medicine From German researchers on the use of CAR T therapy against SLE (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 B cell-resistant designs. B cells are the antibody-producing cells of the immune system, and in lupus, B cells arise that attack the patient’s organs and tissues.

In the German study, patients – ; five guys -; Did not benefit from standard lupus treatments. However, 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 cleared out their existing B cells. (Cancer patients would later need to be injected with human antibodies purified from healthy volunteers, to maintain some antibody immunity.) Most importantly, all patients remained in remission during the follow-up period of up to a year, and unlike cancer patients, lupus patients experienced a return of their B cells, which are naturally replenished from blood stem cells in the bone marrow.

Becker and Yoon note in their comment that although the results of the German study need to be confirmed with larger studies and long-term follow-up, they are very promising-; In fact, they suggest that lupus could be an easier target for CAR T than B-cell carcinomas.

The disease driving B cells are less numerous in lupus. Thus, effective CAR T therapy for this autoimmune disease may require a much lower dose which greatly reduces the problem of immunological side effects.”


Daniel Becker, PhD student in cell and molecular biology, Perelman School of Medicine, University of Pennsylvania

source:

Journal reference:

Baker, DJ & June, CH, (2022) CAR T therapy expands its scope to autoimmune diseases. cell. doi.org/10.1016/j.cell.2022.10.026.



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