【ipsc衍生血小板的首次人体临床试验的经验教训:旨在了解血小板的生物发生】。

Koji Eto
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引用次数: 0

摘要

iPLAT1研究于2019年至2020年进行,是首个针对iPS细胞衍生血小板产品(iPSC-PLTs)的人体临床试验。研究对象是一名再生障碍性贫血患者,抗hpa -1a抗体诱导的血小板输注难耐,没有匹配的HPA-1b/1b供体。自体ipsc - plt由巨核细胞系imMKCL制造,该细胞系由患者的ipsc建立。ipsc - plt的高效制造是通过结合生物反应器槽内湍流的概念来模拟体内条件来实现的。经过全面的非临床研究,iPLAT1研究作为剂量递增研究进行,并达到了安全性这一主要终点。然而,没有观察到输血后血小板计数的增加,这增加了输血后测量失败或输注ipsc - plt循环缺陷的可能性。从那时起,我和我的研究团队一直在进行逆向转化研究,以改进immkcl,并开发更大规模的制造系统,以改善生物反应器池中的湍流。我们最近也证明了免疫巨核细胞亚群在immkcl中的特性。在此基础上,我们新开始了下一代ipsc - plt的研发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Lessons from the first-in-human clinical trial of iPSC-derived platelets: aiming to understand platelet biogenesis].

The iPLAT1 study was conducted from 2019 to 2020 as the first-in-human clinical trial of iPS cell-derived platelet products (iPSC-PLTs). The subject was a patient with aplastic anemia refractory to anti-HPA-1a antibody-induced platelet transfusions who had no matched HPA-1b/1b donor. Autologous iPSC-PLTs were manufactured from a megakaryocyte cell line, imMKCL, established from the patient's iPSCs. High-efficiency manufacturing of iPSC-PLTs was achieved by incorporating the concept of turbulent flow in bioreactor tanks to mimic in vivo conditions. After comprehensive non-clinical studies, the iPLAT1 study was conducted as a dose-escalation study and achieved the primary endpoint of safety. However, an increase in the platelet count after transfusion was not observed, raising the possibility of a failure in post-transfusion measurement or defective circulation of transfused iPSC-PLTs. Since then, my research team and I have been conducting reverse-translational research to improve imMKCLs and developing a larger-scale manufacturing system to improve turbulent flow in bioreactor tanks. We have also recently demonstrated properties of subset of immune megakaryocytes in imMKCLs. Building upon such efforts, we have newly begun R&D for next-generation iPSC-PLTs.

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