Engineering chimeric antigen receptor neutrophils from human pluripotent stem cells for targeted cancer immunotherapy.
Engineering chimeric antigen receptor neutrophils from human pluripotent stem cells for targeted cancer immunotherapy.
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DOI：
10.1016/j.celrep.2022.111128
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发表时间：
2022-07-19
期刊：
影响因子：
8.8
通讯作者：
Bao, Xiaoping
中科院分区：
文献类型：
--
作者：
Chang, Yun;Syahirah, Ramizah;Wang, Xuepeng;Jin, Gyuhyung;Torregrosa-Allen, Sandra;Elzey, Bennett D.;Hummel, Sydney N.;Wang, Tianqi;Li, Can;Lian, Xiaojun;Deng, Qing;Broxmeyer, Hal E.;Bao, Xiaoping
中性粒细胞是循环中最丰富的白色血细胞，与癌症的发生和发展密切相关。健康的原代中性粒细胞通过直接接触和通过产生活性氧物质对各种癌细胞系表现出强效的细胞毒性。然而，由于其半衰期短和对遗传修饰的抗性，中性粒细胞尚未被嵌合抗原受体（汽车）工程化以增强其用于靶向免疫治疗的抗肿瘤细胞毒性。在这里，我们用合成的汽车基因工程改造了人类多能干细胞，并通过实施化学定义的平台将其分化为功能性中性粒细胞。所得CAR嗜中性粒细胞在体外和体内均呈现针对肿瘤细胞的上级和特异性细胞毒性。总的来说，我们建立了一个强大的平台，用于大规模生产CAR中性粒细胞，为基于骨髓细胞的治疗策略铺平了道路，这将促进当前的癌症治疗方法。中性粒细胞是介导促肿瘤和抗肿瘤活性的重要先天免疫细胞。Chang等对人多能干细胞进行遗传工程改造以产生嵌合抗原受体（CAR）嗜中性粒细胞，其显示出上级抗肿瘤活性并改善原位胶质母细胞瘤异种移植模型中的存活。
Neutrophils, the most abundant white blood cells in circulation, are closely related to cancer development and progression. Healthy primary neutrophils present potent cytotoxicity against various cancer cell lines through direct contact and via generation of reactive oxygen species. However, due to their short half-life and resistance to genetic modification, neutrophils have not yet been engineered with chimeric antigen receptors (CARs) to enhance their antitumor cytotoxicity for targeted immunotherapy. Here, we genetically engineered human pluripotent stem cells with synthetic CARs and differentiated them into functional neutrophils by implementing a chemically defined platform. The resulting CAR neutrophils present superior and specific cytotoxicity against tumor cells both in vitro and in vivo. Collectively, we established a robust platform for massive production of CAR neutrophils, paving the way to myeloid cell-based therapeutic strategies that would boost current cancer-treatment approaches. Neutrophils are important innate immune cells that mediate both protumor and antitumor activities. Chang et al. genetically engineer human pluripotent stem cells to produce chimeric antigen receptor (CAR) neutrophils that display superior antitumor activities and improve survival in an in situ glioblastoma xenograft model.
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影响因子：
64.5
作者：
Kalafati L;Kourtzelis I;Schulte-Schrepping J;Li X;Hatzioannou A;Grinenko T;Hagag E;Sinha A;Has C;Dietz S;de Jesus Domingues AM;Nati M;Sormendi S;Neuwirth A;Chatzigeorgiou A;Ziogas A;Lesche M;Dahl A;Henry I;Subramanian P;Wielockx B;Murray P;Mirtschink P;Chung KJ;Schultze JL;Netea MG;Hajishengallis G;Verginis P;Mitroulis I;Chavakis T
通讯作者：
Chavakis T
影响因子：
18.4
作者：
Eruslanov EB;Singhal S;Albelda SM
通讯作者：
Albelda SM
影响因子：
18.9
作者：
Jiang Y;Hoenisch RC;Chang Y;Bao X;Cameron CE;Lian XL
通讯作者：
Lian XL
DOI：
10.1073/pnas.2008112117
发表时间：
2020-09-01
影响因子：
11.1
作者：
Itatani, Yoshiro;Yamamoto, Takamasa;Ferrara, Napoleone
通讯作者：
Ferrara, Napoleone
影响因子：
5.9
作者：
Brok-Volchanskaya, Vera S.;Bennin, David A.;Slukvin, Igor
通讯作者：
Slukvin, Igor