COLLEGE PARK — Researchers at the University of Maryland School of Medicine published a study in Signal Transduction and Targeted Therapy that identifies a method to improve the effectiveness and lifespan of CAR T-cells in treating blood cancers. The study found that blocking the protein cathepsin B improved CAR T-cell function.

CAR T-cell therapy involves genetically engineering a patient's T-cells to specifically target cancer cells, and these modified cells are then reinfused into the patient. Most patients who undergo CAR T-cell therapy experience a relapse of their disease within five years.

The study's senior author was Tim Luetkens, who is an associate professor of microbiology and immunology at the University of Maryland School of Medicine. Kenneth Dietze, a research fellow in the Luetkens laboratory, served as the first author. The researchers observed that CAR T-cells sometimes detach fragments from the surfaces of cancer cells and transfer these fragments to themselves. Luetkens said, "This process makes the CAR T-cells less effective at attacking cancer." Luetkens also serves as director of research and development at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center Fannie Angelos Cellular Therapeutics GMP Lab.

Lab and animal models showed that inhibiting cathepsin B prevented CAR T-cells from detaching these cancer cell fragments. This inhibition extended the active lifespan of the CAR T-cells and increased their tumor-fighting activity in the study models. The researchers used advanced imaging techniques to visually track the CAR T-cells detaching and transferring fragments from cancer cells.

Luetkens said, "Genetically engineered cells are a promising new way to treat cancer and autoimmune diseases. However, scientists are still figuring out how these cells work and how to make them better." Taofeek K. Owonikoko, executive director of the Greenebaum Comprehensive Cancer Center and Kevin Cullen Distinguished Professor in Oncology at the University of Maryland School of Medicine, said, "I am proud of UMGCCC's continued innovation in CAR T-therapy. While these findings need to be translated into human clinical trials, this is real progress that could ultimately improve durability and outcomes for our patients."

The center is currently conducting a first-in-human clinical trial for CAR T-cell therapy in patients with recurrent or difficult-to-treat B-cell lymphoma. The current study was a collaboration with the Upadhyaya laboratory at the University of Maryland, College Park. Funding for the research came from the Maryland Department of Health, the National Cancer Institute, the National Institutes of Health, and the American Cancer Society.