生物
NKG2D公司
白细胞介素21
白细胞介素12
NK-92
Janus激酶3
淋巴因子激活杀伤细胞
嵌合抗原受体
细胞生物学
癌症研究
免疫疗法
细胞毒性T细胞
免疫系统
免疫学
癌症免疫疗法
受体
自然杀伤细胞
干细胞
T细胞
体外
生物化学
作者
Ye Li,David Hermanson,Branden S. Moriarity,Dan S. Kaufman
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2018-08-01
卷期号:23 (2): 181-192.e5
被引量:584
标识
DOI:10.1016/j.stem.2018.06.002
摘要
Chimeric antigen receptors (CARs) significantly enhance the anti-tumor activity of immune effector cells. Although most studies have evaluated CAR expression in T cells, here we evaluate different CAR constructs that improve natural killer (NK) cell-mediated killing. We identified a CAR containing the transmembrane domain of NKG2D, the 2B4 co-stimulatory domain, and the CD3ζ signaling domain to mediate strong antigen-specific NK cell signaling. NK cells derived from human iPSCs that express this CAR (NK-CAR-iPSC-NK cells) have a typical NK cell phenotype and demonstrate improved anti-tumor activity compared with T-CAR-expressing iPSC-derived NK cells (T-CAR-iPSC-NK cells) and non-CAR-expressing cells. In an ovarian cancer xenograft model, NK-CAR-iPSC-NK cells significantly inhibited tumor growth and prolonged survival compared with PB-NK cells, iPSC-NK cells, or T-CAR-iPSC-NK cells. Additionally, NK-CAR-iPSC-NK cells demonstrate in vivo activity similar to that of T-CAR-expressing T cells, although with less toxicity. These NK-CAR-iPSC-NK cells now provide standardized, targeted "off-the-shelf" lymphocytes for anti-cancer immunotherapy.
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