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; 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:10.3389/fmed.2023.1166871

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

Front Med (Lausanne). 2023 May 19:10:1166871. doi: 10.3389/fmed.2023.1166871. eCollection 2023.

Authors

Memnon Lysandrou¹, Dionysia Kefala¹, Panayiota Christofi^{1

2}, Nikolaos Savvopoulos¹, Penelope Georgia Papayanni², Rodanthy Theodorellou³, Eleftheria Sagiadinou¹, Vassiliki Zacharioudaki¹, Maria Moukouli³, Dimitrios Tsokanas¹, Georgios Karavalakis², Maria Liga¹, Konstantinos Stavrinos³, Anastasia Papadopoulou², Evangelia Yannaki², Alexandros Spyridonidis¹

Affiliations

¹ Bone Marrow Transplantation Unit and Institute of Cell Therapy, University of Patras, Rio, Greece.
² Gene and Cell Therapy Center, Hematopoietic Cell Transplantation Unit, Hematology Department, "George Papanikolaou" Hospital, Thessaloniki, Greece.
³ Pharmassist Ltd., Athens, Greece.

Abstract

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).

Keywords: HLA-G; adoptive cellular immunotherapy; advanced therapeutic medicinal products (ATMPs); allogeneic hematopoietic cell transplantation; graft versus host disease; hypomethylating agents; regulatory T cells.

Copyright © 2023 Lysandrou, Kefala, Christofi, Savvopoulos, Papayanni, Theodorellou, Sagiadinou, Zacharioudaki, Moukouli, Tsokanas, Karavalakis, Liga, Stavrinos, Papadopoulou, Yannaki and Spyridonidis.