Frontiers in Medicine (May 2023)

Study protocol: Phase I/II trial of induced HLA-G+ regulatory T cells in patients undergoing allogeneic hematopoietic cell transplantation from an HLA-matched sibling donor

  • Memnon Lysandrou,
  • Dionysia Kefala,
  • Panayiota Christofi,
  • Panayiota Christofi,
  • Nikolaos Savvopoulos,
  • Penelope Georgia Papayanni,
  • Rodanthy Theodorellou,
  • Eleftheria Sagiadinou,
  • Vassiliki Zacharioudaki,
  • Maria Moukouli,
  • Dimitrios Tsokanas,
  • Georgios Karavalakis,
  • Maria Liga,
  • Konstantinos Stavrinos,
  • Anastasia Papadopoulou,
  • Evangelia Yannaki,
  • Alexandros Spyridonidis

DOI
https://doi.org/10.3389/fmed.2023.1166871
Journal volume & issue
Vol. 10

Abstract

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Regulatory T-cell (Treg) immunotherapy has emerged as a promising and highly effective strategy to combat graft-versus-host disease (GvHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Both naturally occurring Treg and induced Treg populations have been successfully evaluated in trials illustrating the feasibility, safety, and efficacy required for clinical translation. Using a non-mobilized leukapheresis, we have developed a good manufacturing practice (GMP)-compatible induced Treg product, termed iG-Tregs, that is enriched in cells expressing the potent immunosuppressive human leucocyte antigen-G molecule (HLA-G+). To assess the safety and the maximum tolerable dose (MTD) of iG-Tregs, we conduct a phase I–II, two-center, interventional, dose escalation (3 + 3 design), open-label study in adult patients undergoing allo-HCT from an HLA-matched sibling donor, which serves also as the donor for iG-Treg manufacturing. Herein, we present the clinical protocol with a detailed description of the study rationale and design as well as thoroughly explain every step from patient screening, product manufacturing, infusion, and participant follow-up to data collection, management, and analysis (registered EUDRACT-2021-006367-26).

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