Ganeeva Irina, Zmievskaya Ekaterina, Valiullina Aygul, Kudriaeva Anna, Miftakhova Regina, Rybalov Alexey, Bulatov Emil
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.
Bioengineering (Basel). 2022 Dec 15;9(12):808. doi: 10.3390/bioengineering9120808.
Harnessing the human immune system as a foundation for therapeutic technologies capable of recognizing and killing tumor cells has been the central objective of anti-cancer immunotherapy. In recent years, there has been an increasing interest in improving the effectiveness and accessibility of this technology to make it widely applicable for adoptive cell therapies (ACTs) such as chimeric antigen receptor T (CAR-T) cells, tumor infiltrating lymphocytes (TILs), dendritic cells (DCs), natural killer (NK) cells, and many other. Automated, scalable, cost-effective, and GMP-compliant bioreactors for production of ACTs are urgently needed. The primary efforts in the field of GMP bioreactors development are focused on closed and fully automated point-of-care (POC) systems. However, their clinical and industrial application has not yet reached full potential, as there are numerous obstacles associated with delicate balancing of the complex and often unpredictable cell biology with the need for precision and full process control. Here we provide a brief overview of the existing and most advanced systems for ACT manufacturing, including cell culture bags, G-Rex flasks, and bioreactors (rocking motion, stirred-flask, stirred-tank, hollow-fiber), as well as semi- and fully-automated closed bioreactor systems.
利用人体免疫系统作为能够识别和杀死肿瘤细胞的治疗技术的基础，一直是抗癌免疫疗法的核心目标。近年来，人们越来越关注提高这项技术的有效性和可及性，使其广泛应用于过继性细胞疗法（ACT），如嵌合抗原受体T（CAR-T）细胞、肿瘤浸润淋巴细胞（TIL）、树突状细胞（DC）、自然杀伤（NK）细胞等多种细胞疗法。迫切需要用于生产ACT的自动化、可扩展、具有成本效益且符合GMP标准的生物反应器。GMP生物反应器开发领域的主要工作集中在封闭和全自动的即时护理（POC）系统上。然而，它们的临床和工业应用尚未充分发挥潜力，因为在复杂且往往不可预测的细胞生物学与精确性和全流程控制需求之间的微妙平衡存在诸多障碍。在这里，我们简要概述了用于ACT制造的现有和最先进的系统，包括细胞培养袋、G-Rex培养瓶以及生物反应器（摇摆式、搅拌瓶式、搅拌罐式、中空纤维式），还有半自动和全自动封闭生物反应器系统。
