CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients

doi:10.1038/srep20070

	CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients
	Su, Shu 1,2; Hu, Bian 3; Shao, Jie 1,2; Shen, Bin 4; Du, Juan 1,2; Du, Yinan 3; Zhou, Jiankui 3; Yu, Lixia 1,2; Zhang, Lianru 1,2; Chen, Fangjun 1,2; Sha, Huizi 1,2; Cheng, Lei 1,2; Meng, Fanyan 1,2; Zou, Zhengyun 1,2; Huang, Xingxu3,5 ; Liu, Baorui 1,2
	2016-01-28
发表期刊	SCIENTIFIC REPORTS
ISSN	2045-2322
卷号	6
发表状态	已发表
DOI	10.1038/srep20070
摘要	Strategies that enhance the function of T cells are critical for immunotherapy. One negative regulator of T-cell activity is ligand PD-L1, which is expressed on dentritic cells (DCs) or some tumor cells, and functions through binding of programmed death-1 (PD-1) receptor on activated T cells. Here we described for the first time a non-viral mediated approach to reprogram primary human T cells by disruption of PD-1. We showed that the gene knockout of PD-1 by electroporation of plasmids encoding sgRNA and Cas9 was technically feasible. The disruption of inhibitory checkpoint gene PD-1 resulted in significant reduction of PD-1 expression but didn't affect the viability of primary human T cells during the prolonged in vitro culture. Cellular immune response of the gene modified T cells was characterized by up-regulated IFN-gamma production and enhanced cytotoxicity. These results suggest that we have demonstrated an approach for efficient checkpoint inhibitor disruption in T cells, providing a new strategy for targeting checkpoint inhibitors, which could potentialy be useful to improve the efficacy of T-cell based adoptive therapies.
收录类别	SCI
语种	英语
资助项目	Jiangsu Provincial Program of Medical Science[BL2012001]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000368786900001
出版者	NATURE PUBLISHING GROUP
WOS关键词	ANTIGEN ; BLOCKADE ; GENERATION ; ANTIBODY ; SAFETY
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1936
专题	生命科学与技术学院_PI研究组_黄行许组
通讯作者	Huang, Xingxu; Liu, Baorui
作者单位	1.Nanjing Univ, Sch Med, Drum Tower Hosp, Ctr Comprehens Canc, Nanjing 210008, Peoples R China 2.Nanjing Univ, Clin Canc Inst, Nanjing 210008, Peoples R China 3.Nanjing Univ, Natl Resource Ctr Mutant Mice, MOE Key Lab Model Anim Dis Study, Model Anim Res Ctr, Nanjing 210061, Jiangsu, Peoples R China 4.Nanjing Med Univ, Dept Histol & Embryol, State Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Su, Shu,Hu, Bian,Shao, Jie,et al. CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients[J]. SCIENTIFIC REPORTS,2016,6.
APA	Su, Shu.,Hu, Bian.,Shao, Jie.,Shen, Bin.,Du, Juan.,...&Liu, Baorui.(2016).CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients.SCIENTIFIC REPORTS,6.
MLA	Su, Shu,et al."CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients".SCIENTIFIC REPORTS 6(2016).