Donor Regulatory T-Cell Infusion with Interleukin-2 in Steroid-Refractory Chronic GVHD

By Patrick Daly - Last Updated: June 7, 2022

Jennifer Whangbo and collaborating researchers explored a combination of low-dose interleukin-2 (LD IL-2) and regulatory T cell-enriched lymphocytes (Treg DLI) for the treatment of steroid-refractory (SR) chronic graft-versus-host disease (cGVHD). In their report, published in Blood Advances, the authors proposed that, “infusion of polyclonal healthy donor Tregs followed by expansion with LD IL-2 is safe in patients with SR-cGVHD.”

The study included 25 adult patients with SR-cGVHD who received a single infusion of Treg DLI (sourced from the original stem cell donor) and in vivo Treg expansion using LD IL-2 at a dose of 1 × 106 IU/m2 daily over eight weeks. Treg DLI was initiated at a dose of 0.1 × 106 cells/kg patient and escalated to a maximum dose of 1 × 106 cells/kg.

According to the article, “Treg DLI plus LD IL-2 was well-tolerated and led to partial responses (PR) in 5 of 25 patients (20%) after 8 weeks of therapy.” The authors added that 10 additional patients (40%) achieved stable disease with minor responses that did not meet the criteria for PR. Treg expansion was reportedly similar across all dose levels without significantly altering CD4+ conventional T cell or CD8+ T cell counts. Finally, authors observed that “a subset of DLI-derived Treg clones showed preferential expansion at week eight and long-term persistence one-year post-infusion.”

To the authors’ knowledge, this was the first study to show that a combination of Tregs infusion and LD IL-2 was safe in a population of patients with SR-cGVHD. They proposed that their data serves as “a foundation for future adoptive Treg therapies in the post-transplant setting.”