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非病毒技术可以为 CAR-NK 细胞疗法铺平道路。

Nonviral technologies can pave the way for CAR-NK cell therapy.

机构信息

Goethe University Frankfurt, Department of Pediatrics, Experimental Immunology & Cell Therapy, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.

Frankfurt Cancer Institute, Goethe University, Paul-Ehrlich-Straße 42-44, 60596 Frankfurt am Main, Germany.

出版信息

J Leukoc Biol. 2023 Oct 26;114(5):475-486. doi: 10.1093/jleuko/qiad074.


DOI:10.1093/jleuko/qiad074
PMID:37403203
Abstract

Natural killer cells are a promising platform for cancer immunotherapy. Natural killer cells have high intrinsic killing capability, and the insertion of a chimeric antigen receptor can further enhance their antitumor potential. In first-in-human trials, chimeric antigen receptor-natural killer cells demonstrated strong clinical activity without therapy-induced side effects. The applicability of natural killer cells as an "off-the-shelf" product makes them highly attractive for gene-engineered cell therapies. Traditionally, viral transduction has been used for gene editing; however, the use of viral vectors remains a safety concern and is associated with high costs and regulatory requirements. Here, we review the current landscape of nonviral approaches for chimeric antigen receptor-natural killer cell generation. This includes transfection of vector particles and electroporation of mRNA and DNA vectors, resulting in transient modification and chimeric antigen receptor expression. In addition, using nonviral transposon technologies, natural killer cells can be stably modified ensuring long-lasting chimeric antigen receptor expression. Finally, we discuss CRISPR/Cas9 tools to edit key genes for natural killer cell functionality.

摘要

自然杀伤细胞是癌症免疫疗法的一个有前途的平台。自然杀伤细胞具有很高的内在杀伤能力,而嵌合抗原受体的插入可以进一步增强其抗肿瘤潜力。在首次人体试验中,嵌合抗原受体自然杀伤细胞表现出强烈的临床活性,没有治疗诱导的副作用。自然杀伤细胞作为“现成”产品的适用性使它们成为基因工程细胞疗法的极具吸引力。传统上,病毒转导已用于基因编辑;然而,病毒载体的使用仍然存在安全隐患,并且与高成本和监管要求相关。在这里,我们回顾了用于嵌合抗原受体自然杀伤细胞生成的非病毒方法的现状。这包括载体颗粒的转染和 mRNA 和 DNA 载体的电穿孔,导致瞬时修饰和嵌合抗原受体表达。此外,使用非病毒转座子技术,自然杀伤细胞可以进行稳定修饰,确保嵌合抗原受体的长期表达。最后,我们讨论了用于编辑自然杀伤细胞功能的关键基因的 CRISPR/Cas9 工具。

相似文献

[1]
Nonviral technologies can pave the way for CAR-NK cell therapy.

J Leukoc Biol. 2023-10-26

[2]
A Nonviral piggyBac Transposon-Mediated Method to Generate Large-Scale CAR-NK Cells from Human Peripheral Blood Primary NK Cells.

Methods Mol Biol. 2024

[3]
Use of Cell and Genome Modification Technologies to Generate Improved "Off-the-Shelf" CAR T and CAR NK Cells.

Front Immunol. 2020

[4]
Concurrent transposon engineering and CRISPR/Cas9 genome editing of primary CLL-1 chimeric antigen receptor-natural killer cells.

Cytotherapy. 2022-11

[5]
Non-viral approaches in CAR-NK cell engineering: connecting natural killer cell biology and gene delivery.

J Nanobiotechnology. 2024-9-10

[6]
Chimeric antigen receptor- and natural killer cell receptor-engineered innate killer cells in cancer immunotherapy.

Cell Mol Immunol. 2021-9

[7]
Preclinical Assessment of Suitable Natural Killer Cell Sources for Chimeric Antigen Receptor Natural Killer-Based "Off-the-Shelf" Acute Myeloid Leukemia Immunotherapies.

Hum Gene Ther. 2019-3-18

[8]
Viral and Nonviral Engineering of Natural Killer Cells as Emerging Adoptive Cancer Immunotherapies.

J Immunol Res. 2018-9-17

[9]
Chimeric Antigen Receptor-Engineered Natural Killer (CAR NK) Cells in Cancer Treatment; Recent Advances and Future Prospects.

Stem Cell Rev Rep. 2021-12

[10]
Taking Lessons from CAR-T Cells and Going Beyond: Tailoring Design and Signaling for CAR-NK Cells in Cancer Therapy.

Front Immunol. 2022

引用本文的文献

[1]
Precision sniper for solid tumors: CAR-NK cell therapy.

Cancer Immunol Immunother. 2025-7-24

[2]
Rendering NK Cells Antigen-Specific for the Therapy of Solid Tumours.

Int J Mol Sci. 2025-6-29

[3]
Migration Dynamics of Human NK Cell Preparations in Microchannels and Their Invasion Into Patient-Derived Tissue.

J Cell Mol Med. 2025-4

[4]
Empowering Natural Killer Cells to Combat Acute Myeloid Leukemia: Perspective on CAR-NK Cell Therapy.

Transfus Med Hemother. 2024-10-1

[5]
CRISPR/Cas9 editing of NKG2A improves the efficacy of primary CD33-directed chimeric antigen receptor natural killer cells.

Nat Commun. 2024-9-30

[6]
Engineering of potent CAR NK cells using non-viral Sleeping Beauty transposition from minimalistic DNA vectors.

Mol Ther. 2024-7-3

[7]
CAR-NK Cells Generated with mRNA-LNPs Kill Tumor Target Cells In Vitro and In Vivo.

Int J Mol Sci. 2023-8-29

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