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利用 CRISPR/Cas9 进行 NK 细胞基因重编程以实现癌症免疫治疗

Genetic reprogramming for NK cell cancer immunotherapy with CRISPR/Cas9.

机构信息

Shenzhen Laboratory of Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

University of Chinese Academy of Sciences, Beijing, China.

出版信息

Immunology. 2019 Oct;158(2):63-69. doi: 10.1111/imm.13094. Epub 2019 Aug 14.


DOI:10.1111/imm.13094
PMID:31315144
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6742769/
Abstract

Natural killer cells are potent cytotoxic lymphocytes specialized in recognizing and eliminating transformed cells, and in orchestrating adaptive anti-tumour immunity. However, NK cells are usually functionally exhausted in the tumour microenvironment. Strategies such as checkpoint blockades are under investigation to overcome NK cell exhaustion in order to boost anti-tumour immunity. The discovery and development of the CRISPR/Cas9 technology offer a flexible and efficient gene-editing capability in modulating various pathways that mediate NK cell exhaustion, and in arming NK cells with novel chimeric antigen receptors to specifically target tumour cells. Despite the high efficiency in its gene-editing capability, difficulty in the delivery of the CRISPR/Cas9 system remains a major bottleneck for its therapeutic applications, particularly for NK cells. The current review discusses feasible approaches to deliver the CRISPR/Cas9 systems, as well as potential strategies in gene-editing for NK cell immunotherapy for cancers.

摘要

自然杀伤细胞是一种具有强大细胞毒性的淋巴细胞,专门用于识别和消除转化细胞,并协调适应性抗肿瘤免疫。然而,NK 细胞在肿瘤微环境中通常功能耗竭。目前正在研究检查点阻断等策略,以克服 NK 细胞衰竭,从而增强抗肿瘤免疫。CRISPR/Cas9 技术的发现和发展提供了一种灵活高效的基因编辑能力,可以调节介导 NK 细胞衰竭的各种途径,并为 NK 细胞配备新型嵌合抗原受体,以特异性靶向肿瘤细胞。尽管其基因编辑能力效率很高,但 CRISPR/Cas9 系统的递送仍然是其治疗应用的主要瓶颈,特别是对于 NK 细胞。本综述讨论了递送 CRISPR/Cas9 系统的可行方法,以及用于癌症 NK 细胞免疫治疗的基因编辑的潜在策略。

相似文献

[1]
Genetic reprogramming for NK cell cancer immunotherapy with CRISPR/Cas9.

Immunology. 2019-8-14

[2]
Enhanced NK-92 Cytotoxicity by CRISPR Genome Engineering Using Cas9 Ribonucleoproteins.

Front Immunol. 2020

[3]
ablation with CRISPR/Cas9 enhances cytotoxicity of human placental stem cell-derived NK cells for cancer immunotherapy.

J Immunother Cancer. 2021-3

[4]
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Int J Nanomedicine. 2023

[5]
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Stem Cells Transl Med. 2024-3-15

[6]
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[7]
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[8]
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Cell Immunol. 2021-11

[9]
Use of Cell and Genome Modification Technologies to Generate Improved "Off-the-Shelf" CAR T and CAR NK Cells.

Front Immunol. 2020

[10]
Retroviral Vectors for Cancer Gene Therapy.

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引用本文的文献

[1]
Overcoming Immune Barriers in Allogeneic CAR-NK Therapy: From Multiplex Gene Editing to AI-Driven Precision Design.

Biomolecules. 2025-6-26

[2]
CAR-NK cell therapy: promise and challenges in solid tumors.

Front Immunol. 2025-4-7

[3]
Advancing Natural Killer Cell Therapy: Genetic Engineering Strategies for Enhanced Cancer Immunotherapy.

Ann Lab Med. 2025-3-1

[4]
Revolutionising Cancer Immunotherapy: Advancements and Prospects in Non-Viral CAR-NK Cell Engineering.

Cell Prolif. 2025-4

[5]
Prospects for potential therapy targeting immune‑associated factors in endometriosis (Review).

Mol Med Rep. 2025-3

[6]
Immunological dynamics in MASH: from landscape analysis to therapeutic intervention.

J Gastroenterol. 2024-12

[7]
Intracellular checkpoints for NK cell cancer immunotherapy.

Front Med. 2024-10

[8]
Harnessing the Power of NK Cell Receptor Engineering as a New Prospect in Cancer Immunotherapy.

Pharmaceutics. 2024-8-29

[9]
Current approaches in glioblastoma multiforme immunotherapy.

Clin Transl Oncol. 2024-7

[10]
Chimeric antigen receptor-based natural killer cell immunotherapy in cancer: from bench to bedside.

Cell Death Dis. 2024-1-15

本文引用的文献

[1]
CRISPR/Cas9-mediated PD-1 disruption enhances human mesothelin-targeted CAR T cell effector functions.

Cancer Immunol Immunother. 2018-12-6

[2]
Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells.

Cell. 2018-11-29

[3]
Disruption of PD-1 Enhanced the Anti-tumor Activity of Chimeric Antigen Receptor T Cells Against Hepatocellular Carcinoma.

Front Pharmacol. 2018-10-1

[4]
In vivo CRISPR editing with no detectable genome-wide off-target mutations.

Nature. 2018-9-12

[5]
CRISPR-Cas guides the future of genetic engineering.

Science. 2018-8-31

[6]
An APOBEC3A-Cas9 base editor with minimized bystander and off-target activities.

Nat Biotechnol. 2018-7-30

[7]
Generation of Knock-out Primary and Expanded Human NK Cells Using Cas9 Ribonucleoproteins.

J Vis Exp. 2018-6-14

[8]
Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity.

Nat Immunol. 2018-6-18

[9]
Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA induces homology-directed DNA repair.

Nat Biomed Eng. 2017

[10]
Nonviral gene editing via CRISPR/Cas9 delivery by membrane-disruptive and endosomolytic helical polypeptide.

Proc Natl Acad Sci U S A. 2018-4-23

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