Abstract: “The adoptive transfer of regulatory T cells (Treg) has acquired a growing interest for controlling exacerbated inflammatory responses due to their suppressive capabilities. Current protocols utilizing Treg derived from adult peripheral blood face challenges in terms of limited Treg recovery and reduced quality.
We proposed the use of discarded human thymuses obtained during pediatric cardiac surgeries as a novel source of Treg for cellular therapy. This approach overcomes the limitations of current Treg sources and allows for the isolation of a substantial number of undifferentiated Treg. We developed a novel good manufacturing practice (GMP) protocol to obtain massive quantities of highly pure and suppressive thyTreg cells from the pediatric thymus. These cells demonstrate a very high viability and purity, as well as stability under proinflammatory conditions. Furthermore, thyTreg cells exhibit a high suppressive capacity, inhibiting more than 75% of the proliferation of activated CD4+ and CD8+ T cells in vitro at a thyTreg:responder cells ratio of 1:1. We started a first-in-human phase I/II clinical trial to assess the safety, feasibility, and efficacy of autologous thyTreg administration in children undergoing heart transplantation worldwide. The substantial quantity and exceptional quality of thyTreg cells, along with the unique features of the final product, enable the preparation of numerous doses from a single thymus with enhanced therapeutic properties, which could establish a new paradigm in the treatment of inflammatory diseases.”
Brief CV: Rafael holds a PhD in Medicine and Surgery from the Universidad Autónoma of Madrid and a PhD in Biology from the Universidad Complutense of Madrid, receiving in both cases the Extraordinary PhD Award. His research career has focused on the field of immuno-pediatrics with a clear translational approach.
Rafael is the Funding Chief of the Laboratory of Immune-regulation at the “Gregorio Marañón” Health Research Institute (IISGM) of Madrid (Spain). The research work of his group focuses on the study of immune homeostasis and the development of cell therapies to induce immune tolerance in the context of different diseases associated with immune hyperactivation. As a result of his research, the group has initiated a pioneering clinical trial to prevent rejection in transplanted children by means of a cell therapy with Treg obtained from the patient’s thymic tissue.
Rafael has obtained more than 25 national and international grants and is the author of more than 80 indexed publications including articles in journals such as New England Journal of Medicine, American Journal of Transplantation, Frontiers Immunology, etc.
More recently, Rafael founded in 2022 the biotechnology company THYTECH, whose objective is to make cutting-edge technology and research in immunology available to patients.