Mizukami Amanda, Swiech Kamilla
Center for Cell-Based Therapy CTC, Regional Blood Center of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Methods Mol Biol. 2020;2086:139-150. doi: 10.1007/978-1-0716-0146-4_10.
Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the immunotherapy field with high rate complete responses especially for hematological diseases. Despite the diversity of tumor specific-antigens, the manufacturing process is consistent and involves multiple steps, including selection of T cells, activation, genetic modification, and in vitro expansion. Among these complex manufacturing phases, the choice of culture system to generate a high number of functional cells needs to be evaluated and optimized. Flasks, bags, and rocking motion bioreactor are the most used platforms for CAR-T cell expansion in the current clinical trials but are far from being standardized. New processing options are available and a systematic effort seeking automation, standardization and the increase of production scale, would certainly help to bring the costs down and ultimately democratize this personalized therapy. In this review, we describe different cell expansion platforms available as well as the quality control requirements for clinical-grade production.
嵌合抗原受体（CAR）-T细胞疗法彻底改变了免疫治疗领域，尤其是对血液疾病具有很高的完全缓解率。尽管肿瘤特异性抗原多种多样，但制造过程是一致的，涉及多个步骤，包括T细胞的选择、激活、基因改造和体外扩增。在这些复杂的制造阶段中，需要评估和优化用于产生大量功能细胞的培养系统的选择。烧瓶、袋子和摇摆运动生物反应器是目前临床试验中用于CAR-T细胞扩增最常用的平台，但远未标准化。新的处理选项已经出现，寻求自动化、标准化和扩大生产规模的系统性努力肯定有助于降低成本，并最终使这种个性化治疗得以普及。在这篇综述中，我们描述了可用的不同细胞扩增平台以及临床级生产的质量控制要求。
