期刊
ONCOTARGET
卷 7, 期 7, 页码 7563-7577出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6927
关键词
regulatory T cells; tolerance; Immunotherapy; Immunosuppression; liver transplantation; Immunology and Microbiology Section; Immune response; Immunity
资金
- MRC Center for Transplantation
- British Heart Foundation (BHF)
- King's College London
- UK-MRC [MR/J006742/1]
- NIHR Biomedical Research Center at Guy's and Si Thomas' NHS Foundation Trust and King's College London
- British Heart Foundation [RG/13/12/30395] Funding Source: researchfish
- Medical Research Council [MR/L022699/1, G1002000, MR/L008890/1, MR/J006742/1, MR/K025538/1] Funding Source: researchfish
- National Institute for Health Research [ACF-2015-21-006] Funding Source: researchfish
- MRC [G1002000, MR/L022699/1, MR/K025538/1, MR/L008890/1] Funding Source: UKRI
Strategies to prevent organ transplant rejection whilst minimizing long-term immunosuppression are currently under intense investigation with regulatory T cells (Tregs) nearing clinical application. The clinical trial, ThRIL, recently commenced at King's College London, proposes to use Treg cell therapy to induce tolerance in liver transplant recipients, the success of which has the potential to revolutionize the management of these patients and enable a future of drug-free transplants. This is the first report of the manufacture of clinical grade Tregs from prospective liver transplant recipients via a CliniMACS-based GMP isolation technique and expanded using anti-CD3/CD28 beads, IL-2 and rapamycin. We report the enrichment of a pure, stable population of Tregs (> 95% CD4(+)CD25(+)FOXP3(+)), reaching adequate numbers for their clinical application. Our protocol proved successful in, influencing the expansion of superior functional Tregs, as compared to freshly isolated cells, whilst also preventing their conversion to Th17 cells under pro-inflammatory conditions. We conclude with the manufacture of the final Treg product in the clinical research facility (CRF), a prerequisite for the clinical application of these cells. The data presented in this manuscript together with the much-anticipated clinical results from ThRIL, will undoubtedly inform the improved management of the liver transplant recipient.
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