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Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
Published on: March 14, 2011
Expanded antigen-specific donor regulatory T cells for GVHD prevention
Joseph A Pidala1, Nicoletta Cieri2, Michael J Schell3
1H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States.
Blood
|June 20, 2026
Summary
Infusing expanded donor regulatory T cells (Treg) with sirolimus safely prevents graft-versus-host disease (GVHD) after hematopoietic cell transplantation. These Treg cells persist and expand post-transplant, showing promise for GVHD prevention.
Area of Science:
- Immunology
- Transplantation Medicine
- Cell Therapy
Background:
- Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation (HCT), often caused by minor histocompatibility antigen (mHAg)-specific T cells.
- Current GVHD prophylaxis strategies have limitations, necessitating novel approaches to improve patient outcomes.
- Regulatory T cells (Treg) play a crucial role in immune tolerance and GVHD suppression.
Purpose of the Study:
- To evaluate the safety and preliminary efficacy of infusing expanded mHAg-specific donor regulatory T cells (Treg) combined with sirolimus for GVHD prevention in HCT recipients.
- To determine the maximum tolerated dose (MTD) of expanded donor Treg cells.
- To assess the in vivo persistence and expansion of infused Treg cells post-HCT.
Main Methods:
- A phase I clinical trial using a 3+3 design to escalate doses of expanded mHAg-specific donor Treg cells (0.5 to 4 x 10^5/kg).
- Patients received Treg infusion on day -2 along with sirolimus-based pharmacologic prophylaxis.
- Dose-limiting toxicities (DLTs) were monitored, and secondary endpoints included GVHD incidence, survival, and Treg cell kinetics using TCR-Seq.
Main Results:
- No dose-limiting toxicities were observed, establishing 4 x 10^5/kg as the maximum tolerated dose (MTD).
- The cumulative incidence of grade II-IV acute GVHD at day 100 was 13%, and NIH moderate/severe chronic GVHD by 3 years was 20%.
- Overall survival was 73%, and infused Treg cells demonstrated successful in vitro expansion, post-HCT lineage fidelity, persistence, and in vivo expansion.
Conclusions:
- Expanded mHAg-specific donor Treg cell infusion is a safe and promising strategy for preventing GVHD in HCT.
- The infused Treg cells exhibit durable persistence and expansion in vivo, supporting their therapeutic potential.
- This translational approach offers a novel cellular therapy for improving HCT outcomes by mitigating GVHD.
