Study protocol: Phase I/II trial of induced HLA-G

Area of Science:

• Immunology and Transplantation Medicine
• Cellular Therapy Development

Background:

• Regulatory T-cell (Treg) immunotherapy is a leading strategy for mitigating graft-versus-host disease (GvHD) post allogeneic hematopoietic cell transplantation (allo-HCT).
• Previous trials have confirmed the feasibility, safety, and efficacy of Treg-based therapies, paving the way for clinical application.
• A novel GMP-compatible induced Treg product, iG-Tregs, has been developed, characterized by enrichment of HLA-G+ cells known for potent immunosuppression.

Purpose of the Study:

• To evaluate the safety and determine the maximum tolerable dose (MTD) of the novel iG-Treg cellular therapy.
• To assess the feasibility of using a GMP-compatible induced Treg product derived from non-mobilized leukapheresis in patients undergoing allo-HCT.

Main Methods:

• A Phase I-II, two-center, interventional, dose-escalation (3+3 design) open-label clinical study.
• Adult patients undergoing allo-HCT from an HLA-matched sibling donor, who also serves as the donor for iG-Treg manufacturing, are enrolled.
• The protocol details patient screening, iG-Treg manufacturing, infusion procedures, participant follow-up, and data collection/management.

Main Results:

• This abstract presents the clinical protocol, not the study results.
• The study is designed to establish the safety profile and MTD of iG-Tregs.
• Data collection and analysis will provide insights into the therapeutic potential of HLA-G+ enriched iG-Tregs.

Conclusions:

• The presented protocol outlines a rigorous approach to evaluating a novel Treg immunotherapy for GvHD prevention.
• Successful completion of this trial could establish iG-Tregs as a safe and effective treatment option for allo-HCT recipients.
• The study aims to advance Treg-based therapies by defining the safety and dosage parameters for clinical use.