Roswell Park Launches Exclusive CD83 CAR T-Cell Clinical Trial for Patients with Relapsed or Refractory AML

Roswell Park Comprehensive Cancer Center has launched an exclusive phase 1 clinical trial of a new chimeric antigen receptor (CAR) T-cell therapy for patients whose acute myeloid leukemia (AML) has relapsed or persisted despite earlier treatment. Developed at Roswell Park, this novel immunotherapy targets the CD83 antigen found on leukemia cells. The new strategy holds promise as a treatment for people whose leukemia returns following hematopoietic stem cell transplant — a group of people currently not eligible for other CAR T-cell clinical trials.

Roswell Park has begun patient recruitment for the study and initiated treatment for the first patient enrolled. Importantly, the new treatment could prove to be a bridge to transplant for AML patients whose leukemia does not go into remission following standard treatment.

“Chemotherapy will not cure relapsed AML,” notes Shernan Holtan, MD, Chief of Blood and Marrow Transplantation at Roswell Park and Principal Investigator of the clinical trial. “The only potential for long-term cure has to come from the immune system.”

T cells are important immune cells that target and destroy viruses, bacteria and cancer cells. In CAR T-cell therapy, the patient’s T cells are collected from the blood and reengineered in the laboratory to produce a protein called a chimeric antigen receptor (CAR) that will help them find and attach themselves to cells carrying a specific protein — in this case, the antigen CD83. The T cells are then multiplied and returned to the patient through an intravenous infusion to mount a super-charged attack on the cancer cells. While other CARs target antigens that are present on both diseased and healthy cells, raising the risk of serious side effects, CD83 is found only on leukemia cells and blasts — immature cells in the bone marrow.

The CD83 CAR T cells will be manufactured in Roswell Park’s GMP Engineering & Cell Manufacturing Facility (GEM) — New York State’s first cell therapy hub, and the largest facility of its kind in the nation.

“We can generate cells for people on demand, in real time, which is very exciting,” says Brian Betts, MD, Vice Chair of Strategic Initiatives in Transplant and Cellular Therapy at Roswell Park and scientific lead of the clinical trial. He and Marco Davila, MD, PhD, Senior Vice President and Associate Director for Translational Research, began developing the CD83 CAR in 2018.

In addition, the CD83 CAR is present on “alloreactive” T cells, which cause graft-versus-host disease (GVHD) — a serious and potentially fatal side effect of a different treatment called allogeneic bone marrow transplant, in which a donor’s healthy stem cells replace the patient’s diseased stem cells. GVHD occurs when the donor’s immune cells perceive the patient’s cells as foreign and attack them.

“Our preclinical work has demonstrated that the CD83 CAR can be used not only to prevent GVHD in those patients, but also to treat it,” says Dr. Betts.

This first-of-its-kind clinical trial of a therapy never before available to patients is made possible by generous donations to the Roswell Park Alliance Foundation and The 11 Day Power Play.

For more information about this study or other Roswell Park clinical trials, please call 1-800-ROSWELL (1-800-767-9355) or send an e-mail to [email protected].