Suck Garnet, Koh Mickey Boon Chai
Health Sciences Authority, Singapore.
Hematol Oncol Stem Cell Ther. 2010;3(3):135-42. doi: 10.1016/s1658-3876(10)50024-4.
Natural killer (NK) cell therapies are emerging worldwide as promising anticancer treatments, exploiting the fast cytolytic action of NK effectors and their potentially broad applicability against a wide range of malignancies. Until recently, clinical protocols have mainly involved freshly isolated NK cells or short- term activated NK cells or lymphokine-activated killer (LAK) cells. However, overall effector numbers and their anticancer potencies remained restricted, which poses a limiting factor to clinical efficacy. Recent developments in the field aim to improve clinical trial designs by increasing effector to target cell ratios in vivo and by application of superior cytotoxic NK effectors. Large-scale production of clinical grade NK cells through long-term activation in ex vivo cultures are another novel means in achieving these goals. However, such procedures require compliance with the strict Good Manufacturing Practice (GMP) regulations to ensure quality and safety of the NK cell product. Although the overall number of new protocols still remains comparably low, some of the protocols are already translated into clinical use. Also striking is the diversity of the different protocols proposed. We highlight in this review the most recent developments in the NK cell field with a focus on long-term NK cell expansion. Critical issues relating to this novel and promising type of therapy are highlighted and discussed.
自然杀伤（NK）细胞疗法正在全球范围内作为一种有前景的抗癌治疗方法兴起，它利用NK效应细胞的快速细胞溶解作用以及其对多种恶性肿瘤潜在的广泛适用性。直到最近，临床方案主要涉及新鲜分离的NK细胞、短期活化的NK细胞或淋巴因子激活的杀伤（LAK）细胞。然而，效应细胞的总数及其抗癌效力仍然有限，这对临床疗效构成了限制因素。该领域的最新进展旨在通过提高体内效应细胞与靶细胞的比例以及应用更具细胞毒性的NK效应细胞来改进临床试验设计。通过体外长期活化大规模生产临床级NK细胞是实现这些目标的另一种新方法。然而，此类程序需要符合严格的药品生产质量管理规范（GMP）法规，以确保NK细胞产品的质量和安全性。尽管新方案的总数仍然相对较少，但其中一些方案已经转化为临床应用。同样引人注目的是所提出的不同方案的多样性。在本综述中，我们重点介绍NK细胞领域的最新进展，尤其关注NK细胞的长期扩增。突出并讨论了与这种新型且有前景的治疗方法相关的关键问题。
