First-in-Human Study of ATreg for GVHD Prevention
Tuettenberg A, Ruhnke L, Schloder J, et al. Gp120-Activated Allogeneic Regulatory T Cells for Prevention of Graft-Versus-Host-Disease: A First-in-Human Trial. Transplantation and Cellular Therapy. 2026; (doi: 10.1016/j.jtct.2026.08.054).
Researchers behind a first-in-human clinical study say their work supports the use of adoptive regulatory T cells (Treg) to combat graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (allo-HCT). The team introduced a cell therapy product assembled from polyclonal Tregs extracted from HLA-unmatched third-party donors. Known as ATreg, generation of the cell therapy product was followed by gp120-mediated activation in the presence of IL-12, a process requiring only 16 hours. Avoiding ex vivo expansion, which when prolonged has contributed to limited utilization of adoptive Treg in the past, supported enhanced suppressive function and raised the possibility of achieving therapeutic results at much lower Treg doses. To assess the safety, tolerability, and toxicity of the product, investigators launched the ATreg-001 trial. The Phase I/II investigation included 10 allo-HCT recipients who, in addition to usual GVHD prophylaxis, received ATreg 5-10 days after transplantation. Hematopoietic engraftment and full donor chimerism were successful in all participants, none of whom experienced infusion-related toxicities or other treatment-related safety concerns. With no grade 3-4 acute GVHD occurring within 100 days of allo-HCT, the study authors believe their solution is promising for GVHD prevention.