Fraser Henrieta, Safinia Niloufar, Grageda Nathali, Thirkell Sarah, Lowe Katie, Fry Laura J, Scottá Cristiano, Hope Andrew, Fisher Christopher, Hilton Rachel, Game David, Harden Paul, Bushell Andrew, Wood Kathryn, Lechler Robert I, Lombardi Giovanna
Division of Transplantation, Immunology and Mucosal Biology, King's College London, London, UK.
The Department of Nephrology and Transplantation, Guy's Hospital, Guy's and St. Thomas NHS Foundation Trust.
Mol Ther Methods Clin Dev. 2018 Jan 31;8:198-209. doi: 10.1016/j.omtm.2018.01.006. eCollection 2018 Mar 16.
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 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% CD4CD25FOXP3 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.
基于调节性T细胞（Treg）的免疫疗法在促进自身免疫和移植中的耐受性方面具有巨大潜力。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）标准的生产流程。在这方面，我们报告了我们在实施符合GMP的稳健流程以扩增临床级Treg方面的研究结果，证明了该开发流程用于生产临床应用最终产品的可行性。这种Treg分离程序确保选择了一个纯Treg群体，该群体在培养36天后经历了300倍的扩增，同时保持超过75%的CD4CD25FOXP3细胞纯度和高于80%的抑制功能。此外，我们报告了最终产品的成功冷冻保存，证明了其表型和功能的维持。本手稿中概述的流程已在ONE研究中实施，这是一项多中心I/IIa期临床试验，在肾移植中研究细胞疗法。
