GP120-Activated Allogeneic Regulatory T Cells for Prevention of Graft-Versus-Host-Disease – A First-In-Human Trial

Regulatory T cells (Tregs) sourced from unrelated, human leukocyte antigen (HLA)-unmatched donors and activated overnight are able to be infused safely following transplant, according to a phase 1/2 trial led by the University Medical Center Mainz, Germany, with collaborators at the University Hospital Dresden, University Hospital Münster, St. Johannes Hospital Dortmund, and the University of Freiburg. Published in Transplantation and Cellular Therapy, the study showcased that this off-the-shelf product was feasible to manufacture and produced no attributable safety signals, opening a route to Treg prophylaxis that does not depend on the stem cell donor.

Acute graft-versus-host disease (aGvHD) remains a leading cause of morbidity following allogeneic hematopoietic cell transplantation (alloHCT), and adoptive Treg transfer has been constrained by donor-specific manufacturing and weeks of ex vivo expansion. The ATreg-001 trial tested ATreg, polyclonal Tregs isolated from standard non-mobilized apheresis of healthy third-party donors and activated for 16 hours with the HIV-1 envelope protein gp120 plus interleukin-2, without expansion. Ten patients received a single infusion of 0.1 to 1.0 × 10⁶ cells/kg on day +10 ± 5 after alloHCT across three dose-escalation cohorts, alongside standard prophylaxis, with serious adverse events within 14 days as the primary endpoint.

Fourteen patients were screened and 10 were treated (median age 58 years, range 46 to 74; 5 female). Products met specification with mean identity 88.78% ± 2.48%, potency 72.47% ± 4.93% FOXP3⁺ cells, and viability above 95%; ATreg suppressed allogeneic T cell proliferation in mixed leukocyte reactions (n = 6, p < 0.01) and in surplus clinical batches (n = 4, p < 0.0001). No infusion-related toxicity occurred. All patients engrafted, with median platelet and neutrophil recovery at 14 and 16 days. Within 100 days, no grade 3 to 4 aGvHD occurred, with the cumulative grade 2 to 4 aGvHD being 10% (1/10; 95% CI, 0.45% to 37.42%), and non-relapse mortality being 0%. The authors thus concluded that these hypothesis-generating results justify larger randomized trials.

Reference:

Tuettenberg A, Ruhnke L, Schlöder J, et al. Gp120-Activated Allogeneic Regulatory T cells for Prevention of Graft-versus-Host-Disease – a First-in-Human Trial. Transplant Cell Ther. 2026. https:doi.org/10.1016/j.jtct.2026.08.054