Oncotarget

Research Papers:

CRISPR knock out of programmed cell death protein 1 enhances anti-tumor activity of cytotoxic T lymphocytes

Zhilong Zhao, Long Shi, Wei Zhang, Jinsheng Han, Shaohui Zhang, Zexian Fu and Jianhui Cai _

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Oncotarget. 2018; 9:5208-5215. https://doi.org/10.18632/oncotarget.23730

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Abstract

Zhilong Zhao1, Long Shi2, Wei Zhang4, Jinsheng Han5, Shaohui Zhang6, Zexian Fu7 and Jianhui Cai1,3

1Department of Surgery, Hebei Medical University, Shijiazhuang, Hebei, China

2Department of Oncology, Hebei Medical University Second Affiliated Hospital, Shijiazhuang, Hebei, China

3Department of Surgery & Oncology, Hebei General Hospital, Shijiazhuang, Hebei, China

4Department of Surgery, Handan Central Hospital, Handan, Hebei, China

5Department of Surgery, Cangzhou Hospital of Traditional Chinese Medicine and Western Medicine Integrated Hebei, Cangzhou, Hebei, China

6Department of Oncology, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, Hebei, China

7Department of Oncology, Hebei University of Engineering Affiliated Hospital, Baoding, Hebei, China

Correspondence to:

Jianhui Cai, email: jianhuicai2002@163.com

Keywords: anti-tumor immunity; CRISPR; cytotoxic T lymphocyte; immune checkpoint; PD-1

Received: July 18, 2017     Accepted: August 27, 2017     Published: December 27, 2017

ABSTRACT

Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that functions to attenuate T cell activation. In this study, we knocked out (KO) PD-1 in cytotoxic T lymphocytes (CTLs) using CRISPR-Cas9 system to evaluate its effect on the anti-tumor activity of the CTLs against multiple myeloma (MM). Results show that PD-1 KO CTLs facilitate apoptosis and caspase activation of the co-cultured MM cells and enhanced MM cell death by 36% compared with the control. PD-1 KO also increased TNF-α and IFN-γ secretion of the CTLs by 2.4 and 1.9-fold respectively. The effectiveness of PD-1 KO in enhancing anti-tumor activity of the CTLs was verified in vivo using mouse xenograft model. The xenografted mice treated with PD-1 KO CTLs demonstrated repressed MM tumor growth and prolonged survival compared with the control group. We conclude that CRISPR-Cas9 is an efficient system to knock out PD-1 from CTLs and PD-1 KO could significantly enhance the anti-tumor activity of CTLs.


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