A Novel Protocol to Produce Massive Amounts of Autologous Thymus-Derived Treg Cells (ThyTreg) to Be Employed as Cellular Therapy in Heart Transplanted Children: A New Paradigm for the Prevention of Graft Rejection
1Laboratory of Immune-regulation, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain, 2Cell Culture Unit, Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain, 3Pediatric Cardiac Surgery Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain, 4Pediatric Cardiology Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
Meeting: 2019 American Transplant Congress
Abstract number: D354
Keywords: Heart/lung transplantation, Pediatric, T cells, Tolerance
Session Information
Session Name: Poster Session D: Tolerance: Clinical Studies
Session Type: Poster Session
Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Immune allograft rejection remains the main obstacle to successful transplants. Although transfer of regulatory T cells (Treg) has acquired growing interest in achieving indefinite graft survival, Treg isolated from peripheral blood showed several limitations. Therefore, we explored the use of thymic tissue as an alternative source of Treg for use as cellular immunotherapy.
*Methods: We have developed a novel GMP-compatible protocol to obtain Treg from thymuses routinely discarded during pediatric cardiac surgery. Quality and safety of the thyTreg product manufactured in the GMP facility have been confirmed. We are waiting for the approval from the Spanish Drug Agency (AEMPS), to initiate at early 2019 the first clinical trial worldwide (phase I/IIa) to evaluate the safety and feasibility of employing autologous thyTreg in children undergoing heart transplantation.
*Results: The thyTreg product obtained with our protocol showed very high purity (>90% of CD25+Foxp3+ cells), viability of >85%, stability under proinflammatory conditions and very high suppressive capacity. Importantly, the number of thyTreg recovered from one thymus reached values of more than 13×109 cells, enough to prepare more than 1000 doses of thyTreg. A single dose of autologous thyTreg will be infused back to the patient after transplantation and the other doses will be cryopreserved for potential future reinfusions.
*Conclusions: Massive amounts of pure, highly suppressive Thy-Treg obtained with our novel GMP-compatible protocol are suitable for use as cellular immunotherapy to prevent rejection in heart-transplanted children. The clinical use of these thyTreg could increase the graft survival and induce indefinite immunological tolerance in transplanted patients.
To cite this abstract in AMA style:
Quirós EBernaldode, López R, Pérez V, Clemente M, Gil-Jaurena J, Camino M, Gil N, Panadero E, Medrano C, Pion M, Correa-Rocha R. A Novel Protocol to Produce Massive Amounts of Autologous Thymus-Derived Treg Cells (ThyTreg) to Be Employed as Cellular Therapy in Heart Transplanted Children: A New Paradigm for the Prevention of Graft Rejection [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/a-novel-protocol-to-produce-massive-amounts-of-autologous-thymus-derived-treg-cells-thytreg-to-be-employed-as-cellular-therapy-in-heart-transplanted-children-a-new-paradigm-for-the-prevention-of-gr/. Accessed May 9, 2025.« Back to 2019 American Transplant Congress