New CAR T-Cell Therapy Shows Promise as ‘Magic Bullet’ for Patients with Relapsed/Refractory AML — Even After Transplant

A phase 1 clinical trial underway exclusively at Roswell Park Comprehensive Cancer Center in Buffalo, N.Y., is evaluating a new chimeric antigen receptor (CAR) T-cell therapy that could dramatically transform the treatment of relapsed or refractory acute myeloid leukemia (AML). It offers a potential cure even for patients who relapsed after hematopoietic stem cell transplant — a population excluded from other CAR T-cell clinical trials — and could serve as a bridge to transplant for those who have been unable to achieve remission.

“Chemotherapy will not cure relapsed AML. The only potential for long-term cure has to come from the immune system,” notes Shernan Holtan, MD, Chief of Blood and Marrow Transplantation and Principal Investigator of the clinical trial, which marks the first time patients will receive CAR T cells engineered to target CD83 proteins.

The CD83 antigen is found on leukemia cells and “blasts,” or immature blood cells — but not healthy hematopoietic stem cells, making this unique among other CARs, which target antigens present on both diseased and healthy cells, raising the risk of myeloid aplasia.

And the CD83 CAR comes with an added benefit: It’s present on alloreactive T cells that cause graft-versus-host disease (GVHD), a serious and potentially fatal side effect of allogeneic transplant.

“Our preclinical work demonstrated that it can be used not only to prevent GVHD but also to treat it,” says Brian Betts, MD, Vice Chair of Strategic Initiatives in Transplant and Cellular Therapy at Roswell Park and scientific lead of the clinical trial (NCT06871410). He and Marco Davila, MD, PhD, Senior Vice President and Associate Director for Translational Research at Roswell, began developing the CD83 CAR in 2018. Their ongoing research is funded in part by the National Institutes of Health (grant #5R01HL167232).

The T cells will be manufactured in the Roswell Park GMP Engineering & Cell Manufacturing Facility (GEM) — New York State’s first cell therapy hub, and the largest academic facility of its kind in the nation. “We can generate cells for people on demand, in real time, which is very exciting,” says Dr. Betts.

Investigators expect to enroll 26 participants; the study is now open and enrolling patients.

Dr. Holtan strongly encourages early referral for this study. “The chemotherapy we have is limited in its efficacy,” she says. “If the first line of chemotherapy doesn’t work, there’s little chance of a second or later line getting us where we want to go. We’d like to see patients who have fewer cumulative toxicities from repeated exposure to chemotherapy.”

Dr. Betts and his colleagues recently reported that CD83 is also present on breast cancer cells, an observation that suggests the new CAR’s value for treating other types of cancer. “We’ve made an ‘armored’ version of the CAR to overcome the immune-suppressive milieu of the tumor microenvironment, so we’re excited about the possibility of bringing this into the solid-tumor environment, too,” he says.

The clinical trial is funded by generous donations to the Roswell Park Alliance Foundation and the 11 Day Power Play.