Engineered Treg Donor Cell Therapy to Prevent Graft-Versus-Host Disease

Abstract Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy limited by graft-versus-host disease (GVHD). Donor regulatory T cells (Tregs) appear to prevent GVHD and promote healthy immunity. We have developed a high-precision Treg cell therapy manufactured from donor mobilized peripheral blood. We conducted an open-label, single-center, phase 2 efficacy study investigating if the use of a precision engineered donor Treg cell therapy improves one-year GVHD-free relapse free survival (GRFS) after myeloablative transplantation. Thirty-three patients with HLA-matched donors were enrolled. All donor Treg cell products were successfully manufactured and administered fresh within 72 hours. One-year incidence of acute grade III-IV GVHD of 6%, moderate to severe chronic GVHD of 7% and non-relapse mortality rate of 6%. The primary endpoint of significantly improved one-year GRFS was achieved at 67% for HLA-matched patients compared to a predicted 40% (p < 0.002). Trial participants had a reduced incidence of GVHD and improved GRFS, as compared to rates common to highly variable unmanipulated donor grafts and multi-agent immune suppression.