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Abstract：
Allogeneic natural killer (NK) cell therapy has been effective in treating cancer. Many studies have tested NK cell therapy using human pluripotent stem cells (hPSCs). However, the impacts of the origin of PSC-NK cells on competence are unclear. In this study, several types of hPSCs, including human-induced PSCs (hiPSCs) generated from CD34+, CD3-CD56+, and CD56- cells in umbilical cord blood (UCB), three lines of human embryonic stem cells (hESCs, ES-1. ES-2 and ES-3) and MHC I knockout (B2M-KO)-ESCs were used to differentiate into NK cells and their capacities were analyzed. All PSC types could differentiate into NK cells. Among the iPSC-derived NK cells (iPSC-NKs) and ESC-derived NK cells (ES-NKs), 34+ iPSCs and ES-3 had a higher growth rate and cytotoxicity, respectively, ES-3 also showed better efficacy than 34+ iPSCs. B2M-KO was similar to the wild type. These results suggest that the screening for differentiation of PSCs into NK cells prior to selecting the PSC lines for the development of NK cell immunotherapy is an essential process for universal allotransplantation, including the chimeric antigen receptor (CAR).
摘要：
同种异体自然杀伤（NK）细胞疗法已有效治疗癌症。许多研究已经测试了使用人多能干细胞(hPSC)的NK细胞疗法。然而,PSC-NK细胞来源对能力的影响尚不清楚.在这项研究中,几种类型的hPSC，包括从CD34+产生的人诱导的PSC（hiPSC），CD3-CD56+,脐带血（UCB）中的CD56-细胞，三种人类胚胎干细胞系(hESCs，ES-1.ES-2和ES-3）和MHCI敲除（B2M-KO）-ESC用于分化成NK细胞并分析其能力。所有PSC类型均可分化成NK细胞。在iPSC来源的NK细胞（iPSC-NKs）和ESC来源的NK细胞（ES-NKs）中，34+iPSCs和ES-3有较高的生长速率和细胞毒性,分别,ES-3也显示出比34+iPSC更好的功效。B2M-KO与野生型相似。这些结果表明，在选择用于开发NK细胞免疫治疗的PSC系之前，筛选PSC分化成NK细胞是通用同种异体移植的重要过程。包括嵌合抗原受体(CAR)。
