Development, functional characterization and validation of methodology for GMP-compliant manufacture of phagocytic macrophages: A novel cellular therapeutic for liver cirrhosis.
Development, functional characterization and validation of methodology for GMP-compliant manufacture of phagocytic macrophages: A novel cellular therapeutic for liver cirrhosis.
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GMP兼容吞噬巨噬细胞生产的方法的发展，功能表征和验证：一种新型的细胞肝硬化细胞治疗。
DOI：
10.1016/j.jcyt.2017.05.009
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发表时间：
2017-09
期刊：
影响因子：
4.5
通讯作者：
Campbell JDM
中科院分区：
文献类型：
--
作者：
Fraser AR;Pass C;Burgoyne P;Atkinson A;Bailey L;Laurie A;W A McGowan N;Hamid A;Moore JK;Dwyer BJ;Turner ML;Forbes SJ;Campbell JDM
自体巨噬细胞疗法代表了治疗严重进行性肝硬化的一个潜在的重大治疗进展。在相关模型中，巨噬细胞的施用已显示出减少炎症并驱动纤维化瘢痕分解和组织修复。这种治疗方法的安全性和可行性正在首次人体试验中进行评估（MAcroplasty Therapy for liver CirrHosis [MATCH]试验）。我们概述了GMP生产的开发和验证阶段。这包括使用CliniMACS Prodigy细胞分选系统分离CD 14+细胞;优化巨噬细胞培养条件，评估细胞特性、产品纯度、功能能力和确定最终细胞产品的稳定性。符合GMP的巨噬细胞产物具有高水平的纯度和活力，并具有一致的表型特征，表达高水平的成熟巨噬细胞标志物25 F9和CD 206以及低水平的CCR 2。巨噬细胞表现出有效的吞噬能力，组成性地定向于抗炎特征，并保持对细胞因子和TLR刺激的响应。工艺验证表明，辅料中的细胞产物具有显著耐用性，在收获后长达48小时内始终符合活力和表型放行标准。这是第一份验证大规模、完全符合良好生产规范的自体巨噬细胞治疗产品用于肝硬化潜在治疗的报告。表型和功能测定证实，这些细胞在功能上保持活力长达48小时，从而在向患者给药时具有显著的灵活性。
Autologous macrophage therapy represents a potentially significant therapeutic advance for the treatment of severe progressive liver cirrhosis. Administration of macrophages has been shown to reduce inflammation and drive fibrotic scar breakdown and tissue repair in relevant models. This therapeutic approach is being assessed for safety and feasibility in a first-in-human trial (MAcrophages Therapy for liver CirrHosis [MATCH] trial). We outline the development and validation phases of GMP production. This includes use of the CliniMACS Prodigy cell sorting system to isolate CD14+ cells; optimizing macrophage culture conditions, assessing cellular identity, product purity, functional capability and determining the stability of the final cell product. The GMP-compliant macrophage products have a high level of purity and viability, and have a consistent phenotypic profile, expressing high levels of mature macrophage markers 25F9 and CD206 and low levels of CCR2. The macrophages demonstrate effective phagocytic capacity, are constitutively oriented to an anti-inflammatory profile and remain responsive to cytokine and TLR stimulation. The process validation shows that the cell product in excipient is remarkably robust, consistently passing the viability and phenotypic release criteria up to 48 hours after harvest. This is the first report of validation of a large-scale, fully Good Manufacturing Practice–compliant, autologous macrophage cell therapy product for the potential treatment of cirrhosis. Phenotypic and functional assays confirm that these cells remain functionally viable for up to 48 h, allowing significant flexibility in administration to patients.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.5
作者：
Eyrich, Matthias;Schreiber, Susanne C.;Van Gool, Stefaan W.
通讯作者：
Van Gool, Stefaan W.
良好的制造实践实践的同种异体爱泼斯坦 - 巴尔病毒（EBV）特异性细胞毒性细胞库的建立和运行，用于治疗与EBV相关的淋巴增生性疾病。
影响因子：
6.5
作者：
Vickers MA;Wilkie GM;Robinson N;Rivera N;Haque T;Crawford DH;Barry J;Fraser N;Turner DM;Robertson V;Dyer P;Flanagan P;Newlands HR;Campbell J;Turner ML
通讯作者：
Turner ML
DOI：
10.1073/pnas.1302168110
发表时间：
2013-04-16
影响因子：
11.1
作者：
Bird, Thomas G.;Lu, Wei-Yu;Forbes, Stuart J.
通讯作者：
Forbes, Stuart J.
影响因子：
7.4
作者：
Burger, Maximilian;Thiounn, Nicolas;Sherman, Jeff
通讯作者：
Sherman, Jeff