A Rapamycin-Based GMP-Compatible Process for the Isolation and Expansion of Regulatory T Cells for Clinical Trials.
A Rapamycin-Based GMP-Compatible Process for the Isolation and Expansion of Regulatory T Cells for Clinical Trials.
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DOI：
10.1016/j.omtm.2018.01.006
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发表时间：
2018-03-16
期刊：
影响因子：
--
通讯作者：
Lombardi G
中科院分区：
文献类型：
--
作者：
Fraser H;Safinia N;Grageda N;Thirkell S;Lowe K;Fry LJ;Scottá C;Hope A;Fisher C;Hilton R;Game D;Harden P;Bushell A;Wood K;Lechler RI;Lombardi G
基于调节性T细胞（Treg）的免疫疗法的概念在促进自身免疫和移植耐受方面具有巨大的潜力。Treg细胞疗法的临床转化需要满足严格的药品生产质量管理规范（GMP）标准的生产工艺。在这方面，我们报告了我们关于实施一种稳健的GMP合规工艺以体外扩增临床级TdR的研究结果，证明了该开发工艺用于生产临床应用最终产品的可行性。该Treg分离程序确保选择在培养36天后经历300倍扩增的纯Treg群体，同时保持大于75%CD4 + CD 25 + FOXP 3+细胞的纯度和大于80%的抑制功能。此外，我们报告了最终产品的成功冷冻保存，证明了表型和功能的维持。本手稿中概述的过程已在ONE研究中实施，这是一项多中心I/IIa期临床试验，其中研究了肾移植中的细胞治疗。
The concept of regulatory T cell (Treg)-based immunotherapy has enormous potential for facilitating tolerance in autoimmunity and transplantation. Clinical translation of Treg cell therapy requires production processes that satisfy the rigors of Good Manufacturing Practice (GMP) standards. In this regard, we report our findings on the implementation of a robust GMP compliant process for the ex vivo expansion of clinical grade Tregs, demonstrating the feasibility of this developed process for the manufacture of a final product for clinical application. This Treg isolation procedure ensured the selection of a pure Treg population that underwent a 300-fold expansion after 36 days of culture, while maintaining a purity of more than 75% CD4+CD25+FOXP3+ cells and a suppressive function of above 80%. Furthermore, we report the successful cryopreservation of the final product, demonstrating the maintenance of phenotype and function. The process outlined in this manuscript has been implemented in the ONE study, a multicenter phase I/IIa clinical trial in which cellular therapy is investigated in renal transplantation.
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影响因子：
14.2
作者：
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通讯作者：
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影响因子：
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DOI：
10.2215/cjn.12931212
发表时间：
2013-07-31
影响因子：
9.8
作者：
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通讯作者：
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影响因子：
7.7
作者：
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通讯作者：
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