Clinical grade production of IL-10 producing regulatory Tr1 lymphocytes for cell therapy of chronic inflammatory diseases
Clinical grade production of IL-10 producing regulatory Tr1 lymphocytes for cell therapy of chronic inflammatory diseases
复制标题
DOI：
10.1016/j.intimp.2009.01.032
复制
发表时间：
2009-05-01
影响因子：
5.6
通讯作者：
Foussat, Arnaud
中科院分区：
文献类型：
--
作者：
Brun, Valerie;Bastian, Herve;Foussat, Arnaud
产生IL-10的调节性1型（Tr1）细胞是CD4（+）调节性细胞的一个亚群，能够阻止体外旁观者t细胞增殖并治愈小鼠慢性结肠炎。为了评估Tr1细胞治疗严重克罗恩病患者的I/IIa期临床试验的疗效和耐受性，我们设置了一个可重复的制造工艺，用于GMP生产人类卵清蛋白特异性Tr1细胞。用于tr1细胞生产的程序包括使用果蝇来源的人工抗原提呈细胞转染特定的刺激分子。人类细胞治疗产品的特性表明，体外抑制t细胞增殖的活性依赖于IL-10和tgf - β的产生。制造的Tr1细胞显示包括Foxp3， GITR和CTLA-4表面表达的调节性表型。人类Tr1细胞产品的体外毒性研究表明，使用这些调节性Tr1淋巴细胞进行细胞治疗具有安全性。(C) 2009年Elsevier B.V.出版
IL-10 producing regulatory type 1 (Tr1) cells represents a subpopulation of CD4(+) regulatory cells able to prevent in vitro bystander T-cell proliferation and to cure ongoing chronic colitis in mice. In order to assess the efficacy and tolerance of Tr1 cell therapy in a Phase I/IIa clinical trial in patients displaying severe Crohn's disease, we set tip a reproducible manufacturing process for the GMP production of human ovalbumin specific Tr1 cells. Procedures used for Tr1-cell production include the use of Drosophila derived artificial Antigen Presenting Cells transfected with specific stimulatory molecules. Characterization of the human cell therapy product shows an in vitro suppressive activity on T-cell proliferation dependent on the production of both IL-10 and TGF-beta. Manufactured Tr1 cells display a regulatory phenotype including Foxp3, GITR and CTLA-4 surface expression. In vitro toxicity studies of human Tr1 cell product show a safety profile compatible with the use of these regulatory Tr1 lymphocytes for cell therapy. (C) 2009 Published by Elsevier B.V.