CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients
Su, Shu1,2; Hu, Bian3; Shao, Jie1,2; Shen, Bin4; Du, Juan1,2; Du, Yinan3; Zhou, Jiankui3; Yu, Lixia1,2; Zhang, Lianru1,2; Chen, Fangjun1,2; Sha, Huizi1,2; Cheng, Lei1,2; Meng, Fanyan1,2; Zou, Zhengyun1,2; Huang, Xingxu3,5; Liu, Baorui1,2
AbstractStrategies 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.
Indexed BySCI
Funding ProjectJiangsu Provincial Program of Medical Science[BL2012001]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000368786900001
Original Document TypeArticle
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Cited Times:169[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Corresponding AuthorHuang, Xingxu; Liu, Baorui
Affiliation1.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
Corresponding Author AffilicationSchool of Life Science and Technology
Recommended Citation
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).
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