Minsung Park , Meredith Safford , Jade Scheers , Lora Hammill , Despina Pleitez , Terri Jerbi , Eyram Marcelle Koudji , Shanelle Yelity , Sarah Campion , Mindy M. Miller , Stuart L. Gibb , Alex Sargent
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We found that this automated system could be effectively scaled to 4 times its singular capacity in a 2-h time interval, with variation in cell number and product volume less than 12% across all containers. Analysis of the different sub-lots of the final product revealed high cell viability and consistent T cell phenotype, with a high proportion of effector memory and central memory T cells and low expression of T cell senescence and exhaustion markers. The functionality of the T cell product was compared by measuring cytokine response after restimulation, with secreted levels of effector cytokines like IFN-γ and TNF-α being similar across the different sub-lots. Collectively, these results show that automation can scale up the formulation and fill-finish of a cell manufacturing process while maintaining the phenotype and functionality of the cell product. 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引用次数: 0
摘要
扩大细胞疗法的生产规模既复杂又具有挑战性。在最终配制和灌装到多个容器的过程中保持细胞产品的关键质量属性尤其困难和费力。在这里,我们测试了自动 Finia™ 灌装和整理系统,以高效地扩大 T 细胞产品的配制和灌装整理规模,然后评估了在这一扩大流程中灌装的不同子批次的细胞质量和产品一致性。我们发现,这种自动化系统可以在 2 小时的时间间隔内有效地扩大到其单一容量的 4 倍,所有容器中细胞数量和产品体积的变化均小于 12%。对最终产品不同子批次的分析表明,细胞存活率高,T 细胞表型一致,效应记忆和中心记忆 T 细胞比例高,T 细胞衰老和衰竭标志物表达量低。通过测量再刺激后的细胞因子反应,对 T 细胞产品的功能进行了比较,不同子批次的效应细胞因子(如 IFN-γ 和 TNF-α)分泌水平相似。总之,这些结果表明,在保持细胞产品的表型和功能性的同时,自动化可以扩大细胞生产过程的配制和灌装。更好地了解如何在最终生产过程中保持产品的一致性和质量,对于进一步扩大规模和开发成功的细胞疗法非常重要。
Automation preserves product consistency and quality for the formulation, fill, and finish of T cell-based therapies
Scaling up the manufacture of cell therapies can be complex and challenging. Maintaining critical quality attributes of the cell product during its final formulation and fill-finish into multiple containers can be especially difficult and laborious. Here, we tested the automated Finia™ Fill and Finish System to efficiently scale up the formulation and fill-finish of a T cell product, and then assessed cell quality and product consistency across different sub-lots filled during this expanded process. We found that this automated system could be effectively scaled to 4 times its singular capacity in a 2-h time interval, with variation in cell number and product volume less than 12% across all containers. Analysis of the different sub-lots of the final product revealed high cell viability and consistent T cell phenotype, with a high proportion of effector memory and central memory T cells and low expression of T cell senescence and exhaustion markers. The functionality of the T cell product was compared by measuring cytokine response after restimulation, with secreted levels of effector cytokines like IFN-γ and TNF-α being similar across the different sub-lots. Collectively, these results show that automation can scale up the formulation and fill-finish of a cell manufacturing process while maintaining the phenotype and functionality of the cell product. Better understanding of how to maintain product uniformity and quality during final manufacturing is important to the further scale-up and development of successful cell therapies.
期刊介绍:
The journal brings readers the latest developments in the fast moving field of cellular therapy in man. This includes cell therapy for cancer, immune disorders, inherited diseases, tissue repair and regenerative medicine. The journal covers the science, translational development and treatment with variety of cell types including hematopoietic stem cells, immune cells (dendritic cells, NK, cells, T cells, antigen presenting cells) mesenchymal stromal cells, adipose cells, nerve, muscle, vascular and endothelial cells, and induced pluripotential stem cells. We also welcome manuscripts on subcellular derivatives such as exosomes. A specific focus is on translational research that brings cell therapy to the clinic. Cytotherapy publishes original papers, reviews, position papers editorials, commentaries and letters to the editor. We welcome "Protocols in Cytotherapy" bringing standard operating procedure for production specific cell types for clinical use within the reach of the readership.