Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
Transfus Apher Sci. 2021 Feb;60(1):103065. doi: 10.1016/j.transci.2021.103065. Epub 2021 Jan 10.
Both natural killer (NK) cells and T cells demonstrate potent antitumor responses in many settings. NK cells, unlike T cells, are not the primary mediators of graft-versus-host disease (GVHD). Redirection of T cells with chimeric antigen receptors (CAR) has helped to overcome tumor escape from endogenous T cells. NK cells expressing CARs are a promising new therapy to treat malignancy. Clinical biomanufacturing of CAR NK cells can begin with NK cells derived from many different sources including adult peripheral blood-derived NK cells, cord blood-derived NK cells, cell line-derived NK cells, or stem cell-derived NK cells. Manufacturing protocols may include isolation of NK cells, activation, expansion, and genetic modification to express the chimeric antigen receptors. Clinical trials have tested both unmodified and CAR NK cells with encouraging results. The next stage in clinical development of CAR NK cells represents a highly exciting new frontier in clinical cell therapy as well as understanding basic NK cell biology. The purpose of this review is to provide the reader with a fundamental understanding of the core concepts in CAR NK cell manufacturing, specifically highlighting differences between CAR T cell manufacturing and focusing on future directions in the field.
自然杀伤 (NK) 细胞和 T 细胞在许多情况下均显示出强大的抗肿瘤反应。与 T 细胞不同，NK 细胞不是移植物抗宿主病 (GVHD) 的主要介导者。嵌合抗原受体 (CAR) 转导的 T 细胞已被用于帮助克服内源性 T 细胞的肿瘤逃逸。表达 CAR 的 NK 细胞是治疗恶性肿瘤的一种有前途的新疗法。CAR NK 细胞的临床生物制造可以从许多不同的来源开始，包括成人外周血来源的 NK 细胞、脐血来源的 NK 细胞、细胞系来源的 NK 细胞或干细胞来源的 NK 细胞。制造方案可能包括 NK 细胞的分离、激活、扩增和遗传修饰以表达嵌合抗原受体。临床试验已经测试了未经修饰和 CAR NK 细胞，结果令人鼓舞。CAR NK 细胞临床开发的下一阶段代表了临床细胞治疗以及理解基本 NK 细胞生物学的一个令人兴奋的新前沿。本文的目的是为读者提供对 CAR NK 细胞制造的核心概念的基本理解，特别是强调 CAR T 细胞制造之间的差异，并关注该领域的未来方向。
