Zhu Huang, Kaufman Dan S
Division of Regenerative Medicine, Department of Medicine, University of California San Diego, San Diego, CA, USA.
Blood Sci. 2019 Sep 17;1(1):4-11. doi: 10.1097/BS9.0000000000000023. eCollection 2019 Aug.
Adoptive immunotherapy using immune effector cells has revolutionized cancer treatments with approval of two autologous chimeric antigen receptor (CAR) T cell therapies by the US FDA. Clinical trials using natural killer (NK) cell-based adoptive immunotherapy have been shown to be safe and effective for treatment of multiple malignancies, especially acute myelogenous leukemia. However, most of these trails use primary NK cells isolated from peripheral or cord blood which can have donor-dependent variability and can be challenging to genetic engineer to improve antitumor functions, limiting the widespread use of this promising new therapy. NK cells can now be routinely produced from human pluripotent stem cells, both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). These pluripotent stem cells are homogenous, easy to genetically modify on a clonal level and can be used as unlimited source of NK cells, making them ideal population to develop standardized, off-the-shelf adoptive NK cell therapy products. In this review, we discuss recent advances of obtaining and expanding hESC and iPSC-derived NK cells and novel genetic engineering strategies that are being applied to improve their antitumor functions.
随着美国食品药品监督管理局（FDA）批准两种自体嵌合抗原受体（CAR）T细胞疗法，使用免疫效应细胞的过继性免疫疗法彻底改变了癌症治疗方式。使用基于自然杀伤（NK）细胞的过继性免疫疗法进行的临床试验已证明对多种恶性肿瘤，尤其是急性髓性白血病的治疗是安全有效的。然而，这些试验大多使用从外周血或脐带血中分离的原代NK细胞，这些细胞可能存在供体依赖性变异性，并且对其进行基因工程改造以改善抗肿瘤功能具有挑战性，这限制了这种有前景的新疗法的广泛应用。现在可以从人类多能干细胞，即人类胚胎干细胞（hESC）和诱导多能干细胞（iPSC）中常规生产NK细胞。这些多能干细胞是同质的，易于在克隆水平上进行基因改造，并且可以用作NK细胞的无限来源，使其成为开发标准化、现成的过继性NK细胞治疗产品的理想细胞群体。在这篇综述中，我们讨论了获取和扩增hESC和iPSC来源的NK细胞的最新进展，以及正在应用的新型基因工程策略，以改善它们的抗肿瘤功能。
