Successful expansion of functional and stable regulatory T cells for immunotherapy in liver transplantation.
Successful expansion of functional and stable regulatory T cells for immunotherapy in liver transplantation.
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DOI：
10.18632/oncotarget.6927
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发表时间：
2016-02-16
期刊：
影响因子：
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通讯作者：
Lombardi G
中科院分区：
文献类型：
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作者：
Safinia N;Vaikunthanathan T;Fraser H;Thirkell S;Lowe K;Blackmore L;Whitehouse G;Martinez-Llordella M;Jassem W;Sanchez-Fueyo A;Lechler RI;Lombardi G
预防器官移植排斥反应，同时最大限度地减少长期免疫抑制的策略目前正在密切研究中，调节性T细胞（TCFs）接近临床应用。最近在伦敦国王学院开始的临床试验ThRIL提出使用Treg细胞疗法来诱导肝移植受者的耐受性，其成功有可能彻底改变这些患者的管理并实现无药物移植的未来。这是通过基于CliniMACS的GMP分离技术从预期的肝移植受者中生产临床级THBG的第一份报告，并使用抗CD 3/CD 28珠、IL-2和雷帕霉素进行扩增。我们报告了一个纯的，稳定的人群的富集的T细胞（>95%的CD 4 + CD 25 + FOXP 3+），达到足够的数量，为他们的临床应用。与新鲜分离的细胞相比，我们的方案证明成功地影响了上级功能性Th 17细胞的扩增，同时还防止了它们在促炎条件下转化为Th 17细胞。我们得出结论，在临床研究机构（CRF）中生产最终Treg产品，这是这些细胞临床应用的先决条件。本文中提供的数据以及ThRIL备受期待的临床结果无疑将为肝移植受者的改善管理提供信息。
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.