Immune cells engineered to express a higher level of a protein known as TRAIL destroyed cells that cause graft-versus-host disease (GVHD) in persons with leukemia and other cancers who undergo hematopoietic stem cell transplantation (HSCT). The manipulated immune cells also increased antitumor activity in the recently reported mouse study.
GVHD, a common complication that arises when white blood cells from a donated stem cell graft attack the recipient’s own cells, can be very serious. Current strategies to suppress GVHD also compromise graft-versus-tumor (GVT) responses, explained study authors Arnab Ghosh, MD, PhD, of Memorial Sloan-Kettering Cancer Center, New York, New York, and colleagues in The Journal of Clinical Investigation.
The group had previously shown that the TNF-related apoptosis-inducing ligand, or TRAIL, protein is required for optimal GVT activity against certain malignancies in recipients of allogeneic HSCT (allo-HSCT). The investigators genetically engineered donor T cells to overexpress TRAIL, and implanted the cells into mouse models of allo-HSCT.
The TRAIL-enhanced cells induced apoptosis (programmed cell death) in donor cells set to attack host cells, thereby reducing GVHD. In addition, the engineered cells increased GVT activity. These and other findings from their experiments led Ghosh and associates to conclude that TRAIL-overexpressing donor T cells could potentially enhance the curative potential of allo-HSCT by increasing GVT response and suppressing GVHD.