Global Manufacturing of CAR T Cell Therapy.
Global Manufacturing of CAR T Cell Therapy.
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DOI：
10.1016/j.omtm.2016.12.006
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发表时间：
2017-03-17
期刊：
影响因子：
--
通讯作者：
Keir C
中科院分区：
文献类型：
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作者：
Levine BL;Miskin J;Wonnacott K;Keir C
嵌合抗原受体修饰的T细胞免疫疗法在B细胞恶性肿瘤患者中显示出很高的应答率，嵌合抗原受体T细胞疗法目前正在研究几种血液学和实体肿瘤类型。嵌合抗原受体T细胞是通过从患者血液中取出T细胞并改造细胞以表达嵌合抗原受体而产生的，这种细胞可以重新编程T细胞以靶向肿瘤细胞。随着嵌合抗原受体T细胞疗法进入后期临床试验，并成为更多患者的选择，嵌合抗原受体T细胞制造过程是否符合全球监管要求成为广泛讨论的话题。此外，必须解决将嵌合抗原受体T细胞制造过程从单一机构转移到大规模多地点制造中心的挑战。我们在CD19嵌合抗原受体T细胞治疗CTL019的经验中已经预料到这些问题。在这篇综述中，我们讨论了该技术的细胞处理步骤，包括使用最佳载体进行一致的细胞处理，以及解决将嵌合抗原受体T细胞治疗扩展到全球患者群体的挑战。
Immunotherapy using chimeric antigen receptor-modified T cells has demonstrated high response rates in patients with B cell malignancies, and chimeric antigen receptor T cell therapy is now being investigated in several hematologic and solid tumor types. Chimeric antigen receptor T cells are generated by removing T cells from a patient’s blood and engineering the cells to express the chimeric antigen receptor, which reprograms the T cells to target tumor cells. As chimeric antigen receptor T cell therapy moves into later-phase clinical trials and becomes an option for more patients, compliance of the chimeric antigen receptor T cell manufacturing process with global regulatory requirements becomes a topic for extensive discussion. Additionally, the challenges of taking a chimeric antigen receptor T cell manufacturing process from a single institution to a large-scale multi-site manufacturing center must be addressed. We have anticipated such concerns in our experience with the CD19 chimeric antigen receptor T cell therapy CTL019. In this review, we discuss steps involved in the cell processing of the technology, including the use of an optimal vector for consistent cell processing, along with addressing the challenges of expanding chimeric antigen receptor T cell therapy to a global patient population.