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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-04

AUTHORS

Shu Su, Bian Hu, Jie Shao, Bin Shen, Juan Du, Yinan Du, Jiankui Zhou, Lixia Yu, Lianru Zhang, Fangjun Chen, Huizi Sha, Lei Cheng, Fanyan Meng, Zhengyun Zou, Xingxu Huang, Baorui Liu

ABSTRACT

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-γ 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. More... »

PAGES

20070

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/srep20070

    DOI

    http://dx.doi.org/10.1038/srep20070

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1024675113

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26818188


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