“First-in-Human” Clinical Trial Employing Adoptive Transfer of Autologous Thymus-Derived Treg Cells (Thytreg) to Prevent Graft Rejection in Heart-Transplanted Children

Bernaldo‐de‐Quirós, Esther; Camino, Manuela; Gil-Jaurena, Juan-Miguel; Fernández-Santos, Eugenia; Gil, Nuria; Panadero, Esther; Medrano, Constancio; López, Rocío; Martínez‐Bonet, Marta; Hernández-Flórez, Diana; Levings, Megan K.; West, Lory J; Pion, Marjorie; Correa‐Rocha, Rafael

doi:10.1097/01.tp.0000698356.92326.e1

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interventions such as (1) the election of immunosuppressive drugs with lower impact on Treg; (2) supplementation with vitamin D, which has proven to increase Treg survival 39 and to reduce the risk of acute rejection 40 ; (3) or even a cell therapy with Treg cells, 41,42 could counteract the Treg/Teff imbalance. In adults, adoptive transfer of Treg has provided promising results, 43 and we are currently recruiting patients in a clinical trial of heart transplant children treated with autologous thyTreg, 44 which could establish a new paradigm preventing rejection in the field of solid organ transplantation.…”

Section: Discussionmentioning

confidence: 99%

The Presence of a Marked Imbalance Between Regulatory T Cells and Effector T Cells Reveals That Tolerance Mechanisms Could Be Compromised in Heart Transplant Children

Bernaldo‐de‐Quirós

López‐Abente

Camino

et al. 2021

Transplantation Direct

Self Cite

View full text Add to dashboard Cite

Pediatric TransplantationBackground. Regulatory T cells (Treg) are crucial for the induction and maintenance of graft tolerance. In pediatric heart transplant procedures, the thymus is routinely excised, removing the primary source of T-cell replenishment. Consequently, thymectomy joined to the effects of immunosuppression on the T-cell compartment may have a detrimental impact on Treg values, compromising the intrinsic tolerance mechanisms and the protective role of Treg preventing graft rejection in heart transplant children. Methods. A prospective study including 7 heart transplant children was performed, and immune cell populations were evaluated periodically in fresh peripheral blood at different time points before and up to 3 y posttransplant. Results. Treg counts decreased significantly from the seventh-month posttransplant. Furthermore, there was a significant increase in effector memory and terminally differentiated effector memory T cells coinciding with the fall of Treg counts. The Treg/Teffector ratio, a valuable marker of the tolerance/rejection balance, reached values around 90% lower than pretransplant values. Additionally, a negative correlation between Treg count and T effector frequency was observed. Particularly, when Treg count decreases below 50 or 75 cells/μL in the patients, the increase in the frequency of T effector CD4+ and CD8+, respectively, experiences a tipping point, and the proportion of T-effector cells increases dramatically.Conclusions. These results reveal that interventions employed in pediatric heart transplantation (immunosuppression and thymectomy) could induce, as an inevitable consequence, a dysregulation in the immunologic status characterized by a marked imbalance between Treg and T effector, which could jeopardize the preservation of tolerance during the period with the higher incidence of acute rejection.

show abstract

Section: Discussionmentioning

confidence: 99%

The Presence of a Marked Imbalance Between Regulatory T Cells and Effector T Cells Reveals That Tolerance Mechanisms Could Be Compromised in Heart Transplant Children

Bernaldo‐de‐Quirós

López‐Abente

Camino

et al. 2021

Transplantation Direct

Self Cite

View full text Add to dashboard Cite

show abstract

“…Dijke et al previously reported the potential of discarded human thymuses as an excellent source of Treg to overcome the limitations of peripheral blood in terms of yield, stability, suppressive capacity and survival ( 85 ). Indeed, we have developed a novel GMP-protocol to obtain massive amounts of highly pure, suppressive and stable Treg from thymuses routinely discarded during pediatric cardiac surgeries (thyTreg) after a 7-days culture; being our thyTreg product already approved by the Spanish Drug Agency (AEMPS) to be administered as cell therapy ( 86 ).…”

Section: Thymic Tissue As a New Source Of Treg: An Innovative Approac...mentioning

confidence: 99%

A New Generation of Cell Therapies Employing Regulatory T Cells (Treg) to Induce Immune Tolerance in Pediatric Transplantation

et al. 2022

Self Cite

View full text Add to dashboard Cite

Kidney transplantation is the most common solid organ transplant and the preferred treatment for pediatric patients with end-stage renal disease, but it is still not a definitive solution due to immune graft rejection. Regulatory T cells (Treg) and their control over effector T cells is a crucial and intrinsic tolerance mechanism in limiting excessive immune responses. In the case of transplants, Treg are important for the survival of the transplanted organ, and their dysregulation could increase the risk of rejection in transplanted children. Chronic immunosuppression to prevent rejection, for which Treg are especially sensitive, have a detrimental effect on Treg counts, decreasing the Treg/T-effector balance. Cell therapy with Treg cells is a promising approach to restore this imbalance, promoting tolerance and thus increasing graft survival. However, the strategies used to date that employ peripheral blood as a Treg source have shown limited efficacy. Moreover, it is not possible to use this approach in pediatric patients due to the limited volume of blood that can be extracted from children. Here, we outline our innovative strategy that employs the thymus removed during pediatric cardiac surgeries as a source of therapeutic Treg that could make this therapy accessible to transplanted children. The advantageous properties and the massive amount of Treg cells obtained from pediatric thymic tissue (thyTreg) opens a new possibility for Treg therapies to prevent rejection in pediatric kidney transplants. We are recruiting patients in a clinical trial to prevent rejection in heart-transplanted children through the infusion of autologous thyTreg cells (NCT04924491). If its efficacy is confirmed, thyTreg therapy may establish a new paradigm in preventing organ rejection in pediatric transplants, and their allogeneic use would extend its application to other solid organ transplantation.

show abstract

“First-in-Human” Clinical Trial Employing Adoptive Transfer of Autologous Thymus-Derived Treg Cells (Thytreg) to Prevent Graft Rejection in Heart-Transplanted Children

Cited by 2 publications

References 0 publications

The Presence of a Marked Imbalance Between Regulatory T Cells and Effector T Cells Reveals That Tolerance Mechanisms Could Be Compromised in Heart Transplant Children

The Presence of a Marked Imbalance Between Regulatory T Cells and Effector T Cells Reveals That Tolerance Mechanisms Could Be Compromised in Heart Transplant Children

A New Generation of Cell Therapies Employing Regulatory T Cells (Treg) to Induce Immune Tolerance in Pediatric Transplantation

Contact Info

Product

Resources

About