213.2: Preliminary Results of the First Clinical Trial to Prevent Graft Rejection in Heart Transplant Children Employing a Cellular Therapy With Autologous Treg Obtained From Thymic Tissue (thyTreg)
Notice bibliographique
Résumé
Introduction: Immune allograft rejection remains the main obstacle to successful transplants. Due to their suppressive capacity, regulatory T cell (Treg) therapy is a very promising alternative to prevent rejection and achieve indefinite graft survival. Several clinical trials conducted in adults with peripheral blood Treg demonstrate the safety of the therapy, although its efficacy seems to be limited. To overcome the current barriers and make this therapy effective, we explore a pioneering strategy that employs, as an alternative source of Treg cells, the thymic tissue discarded in pediatric cardiac surgeries. Materials and methods: We developed a novel GMP-compatible protocol to obtain large numbers of Treg cells from pediatric thymic tissue (thyTreg) suitable for use in humans. After confirming the high quality of our therapeutic product and completing preclinical studies, we have started the first worldwide phase I/IIa clinical trial (NCT04924491) that evaluates the safety, feasibility and efficacy of autologous thyTreg in preventing rejection in children undergoing heart transplantation. We employ the thymic tissue removed in heart transplantation surgery to produce therapeutic doses of GMP thyTreg. At day +8±2 post-transplant, a single dose of fresh autologous thyTreg is administered to the patient intravenously (randomized to 10x106 or 20x106 cells/kg), and the remaining thyTreg are cryopreserved. Patients receive their usual immunosuppressants regime (tacrolimus, mycophenolate, short-term corticosteroids) and are clinical and immunological followed up to 2 years post-transplant. A cohort of heart transplant children receiving the same immunosuppressive regime without thyTreg administration is also recruited as the control group. Results: To date, 4 patients have received a thyTreg dose. The four thyTreg products infused showed very high viability (>94%) and purity (CD25+FOXP3+) ≥85% in all cases. The procedure’s safety is confirmed, and the preliminary results obtained in the children treated with this therapy are very encouraging. These results suggest that with a single infusion of thyTreg it is possible to maintain the reserve of Treg cells crucial to prevent rejection, even in these patients who have undergone thymectomy and treated with immunosuppressive therapy. Furthermore, so far, we have yet recruited six more patients in the trial who are still on the heart transplant waiting list, completing the 10 patients planned for this clinical trial. Conclusion: ThyTreg cell constitutes a new therapeutic strategy to prevent rejection in children who have received heart transplants. Preliminary results of our clinical trial confirm the approach’s safety and suggest that it can preserve the peripheral Treg pool. We are confident that the improved quality and amount of thyTreg obtained with this protocol could be a step to induce immunological tolerance and thus achieve the indefinite survival of the transplanted organ. This work was supported by grants from Fundación Familia Alonso (FFAFIBHGM 2019), grants from Instituto de Salud Carlos III (ISCIII) co-financed by FEDER funds (PI21/00189; ICI20/00063; PI18/00495; PI18/00506) and from Comunidad de Madrid (EXOHEP-CM, B2017/BMD-3727).
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».