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一个改进的方法来产生IL-15^+/+/TGFβR2^-/- iPSC衍生的自然杀手细胞使用TALEN

An-Ping Chen¹, Peng Gao¹, Liang Lin¹

¹Cytovia Therapeutics, Inc., Natick, MA, USA.

Cell reports methods

|September 11, 2024

概括

我们开发了一种方法来制造用于癌症免疫治疗的增强诱导多能干细胞 (iPSC). 这些双编辑的iPSCs产生自然杀手 (NK) 细胞,改善了瘤微环境信号的生长和抵抗力.

科学领域:

细胞生物学细胞生物学
免疫学免疫学免疫学
生物技术是生物技术.

背景情况:

诱导多能干细胞 (iPSCs) 对再生医学和免疫疗法至关重要.
增强IPSC衍生的自然杀手 (iNK) 细胞需要进行基因修改以提高它们的有效性.
瘤微环境信号,特别是TGF-β,可以抑制免疫细胞功能.

研究的目的:

建立一个基于 TALEN 的工作流程,用于生成双编辑的 iPSC (IL-15+/+/TGFβR2).
为了产生增强的iPSC衍生自然杀手 (iNK) 细胞用于癌症免疫治疗.
为了确保基因修改最小化对iPSC多能性和功能的影响.

主要方法:

利用TALEN技术在iPSC中进行精确的基因编辑.
在内源B2M促进体下使用细胞谱系促进体来敲进 (KI) IL-15基因.
与Nodal一起开发了一个定制的介质,以保持TGFβR2淘汰 (KO) iPSCs的多能性.

主要成果:

在iNK细胞中实现可溶性IL-15 (sIL-15) 的高表达,在iPSC中表达最小.
成功生成了能够保持多能性的TGFβR2 KO iPSCs.
证明了双编辑iPSCs的高效分化到具有增强自主生长的iNK细胞.
已证实iNK细胞对抑制TGF-β信号产生抵抗力.

结论:

基于TALEN的工作流可以生成双编辑的iPSC,用于增强癌症免疫治疗.
IL-15 KI和TGFβR2 KO的修改改善了iNK细胞的功能和弹性.
这种方法为银行和利用先进的iNK细胞疗法提供了一个强大的平台.

关键词:

B2M B2M B2M B2M B2M B2M B2M B2M B2M B2M B2M B2M B2M B2 CP:癌症生物学癌症生物学在 GUIDE-seqq.这就是TALEN.在TGFβR2中.这是一种抗瘤药物.贝塔-2-微型血球蛋白是一种β-2-微型血球蛋白.基因编辑基因编辑人类诱导的多能干细胞干细胞.从iPSC衍生的细胞疗法.对于 iPSCs 来说,这是一个很好的选择.介质蛋白-15 介质蛋白-15 自然杀手细胞是自然杀手细胞.

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