期刊
FRONTIERS IN IMMUNOLOGY
卷 5, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2014.00016
关键词
hematopoietic stem cell transplantation; haploidentical; IL-10,T regulatory type 1 cells; cell therapy; tolerance
类别
资金
- EU
- Reprogramming the Immune System for the Establishment of Tolerance (RISET1)
- Italian Cancer Association (AIRC)
- Maria Hernandez-Fuentes is part of Indices of Tolerance EU consortium4
- MRC [G0801537, G0600698] Funding Source: UKRI
- Medical Research Council [G0600698, G0801537, MR/J006742/1] Funding Source: researchfish
- Fondazione Telethon Funding Source: Custom
T-cell therapy after hematopoietic stem cell transplantation (HSCT) has been used alone or in combination with immunosuppression to cure hematologic malignancies and to prevent disease recurrence. Here, we describe the outcome of patients with high-risk/advanced stage hematologic malignancies, who received T-cell depleted (TCD) haploidentical-HSCT (haplo-HSCT) combined with donor T lymphocytes pretreated with 11,10 (ALT-TEN trial). 11,10-anergized donor T cells (11,10-DLI) contained T regulatory type 1 (Tr) cells specific for the host alloantigens, limiting donor-vs.-host-reactivity, and memory T cells able to respond to pathogens. 11,10-DLI were infused in 12 patients with the goal of improving immune reconstitution after haplo-HSCT without increasing the risk of graft-versus-host-disease (GvHD). 11,10-DLI led to fast immune reconstitution in five patients. In four out of the five patients, total T-cell counts, TCR-V13 repertoire and T-cell functions progressively normalized after 11,10-DLI. These four patients are alive, in complete disease remission and immunosuppression-free at 7.2 years (median follow-up) after haplo-HSCT. Transient GvHD was observed in the immune reconstituted (IR) patients, despite persistent host-specific hypo-responsiveness of donor T cells in vitro and enrichment of cells with Tr-specific biomarkers in vivo. Gene-expression profiles of IR patients showed a common signature of tolerance. This study provides the first indication of the feasibility of Tr1 cell-based therapy and paves way for the use of these Tr1 cells as adjuvant treatment for malignancies and immune-mediated disorders.
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