University of Maryland School of Medicine researchers announced on June 15 that they have identified a protein target that may improve the effectiveness of CAR T-cell therapy in patients with recurrent or difficult-to-treat blood cancers.
In a study published in Signal Transduction and Targeted Therapy, the research team found that blocking a specific protein in genetically modified immune cells led to increased survival and enhanced tumor-fighting activity in laboratory and animal models. CAR T-cell therapy involves engineering a patient's own T-cells to attack cancer cells before infusing them back into the patient. While this approach can be effective, most patients still experience relapse within five years.
Kenneth Dietze, PhD, first author of the study and research fellow at UMSOM's Luetkens lab, discovered that some CAR T-cells remove small fragments from cancer cell surfaces and attach those fragments to themselves. "This process makes the CAR T-cells less effective at attacking cancer," said Dr. Luetkens, who is also Director of Research and Development at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC) Fannie Angelos Cellular Therapeutics GMP Lab.
The study team found that by blocking cathepsin b—a specific protein—they could prevent this tearing process in CAR T-cells. This allowed the cells to remain active longer and improved their ability to fight cancer.
"I am proud of UMGCCC's continued innovation in CAR T-therapy," said Taofeek K. Owonikoko, MD, PhD, Executive Director of UMGCCC and Kevin Cullen Distinguished Professor in Oncology at UMSOM. "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." Researchers at UMGCCC are currently leading an ongoing first-in-human clinical trial using CAR T-cell therapy for patients with recurrent or difficult-to-treat B-cell lymphoma.
The research was conducted together with the Upadhyaya lab at the University of Maryland, College Park, where advanced imaging techniques were used to observe how CAR T-cells interact with cancer cells.
