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非病毒方法在 CAR-NK 细胞工程中的应用：连接自然杀伤细胞生物学和基因传递。

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

机构信息

School of Pharmacy, Queen's University of Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK.

School of Chemical Sciences, Dublin City University, Collins Avenue, Dublin 9, Ireland.

出版信息

J Nanobiotechnology. 2024 Sep 10;22(1):552. doi: 10.1186/s12951-024-02746-4.

DOI:10.1186/s12951-024-02746-4
PMID:39256765
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11384716/
Abstract

Natural Killer (NK) cells are exciting candidates for cancer immunotherapy with potent innate cytotoxicity and distinct advantages over T cells for Chimeric Antigen Receptor (CAR) therapy. Concerns regarding the safety, cost, and scalability of viral vectors has ignited research into non-viral alternatives for gene delivery. This review comprehensively analyses recent advancements and challenges with non-viral genetic modification of NK cells for allogeneic CAR-NK therapies. Non-viral alternatives including electroporation and multifunctional nanoparticles are interrogated with respect to CAR expression and translational responses. Crucially, the link between NK cell biology and design of drug delivery technologies are made, which is essential for development of future non-viral approaches. This review provides valuable insights into the current state of non-viral CAR-NK cell engineering, aimed at realising the full potential of NK cell-based immunotherapies.

摘要

自然杀伤 (NK) 细胞是癌症免疫疗法的热门候选者，具有强大的先天细胞毒性，并且在嵌合抗原受体 (CAR) 治疗方面优于 T 细胞。人们对病毒载体的安全性、成本和可扩展性表示担忧，这激发了对非病毒替代物用于基因传递的研究。本综述全面分析了用于同种异体 CAR-NK 疗法的 NK 细胞非病毒基因修饰的最新进展和挑战。本文探讨了电穿孔和多功能纳米粒子等非病毒替代物在 CAR 表达和转译反应方面的应用。至关重要的是，本文还探讨了 NK 细胞生物学与药物传递技术设计之间的联系，这对于开发未来的非病毒方法至关重要。本综述为非病毒 CAR-NK 细胞工程的现状提供了有价值的见解，旨在充分发挥基于 NK 细胞的免疫疗法的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a2e/11384716/8ca9b3d7d891/12951_2024_2746_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a2e/11384716/88b190cea5f6/12951_2024_2746_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a2e/11384716/0ae48337146b/12951_2024_2746_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a2e/11384716/0542964e084e/12951_2024_2746_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a2e/11384716/3bb68ea4d86b/12951_2024_2746_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a2e/11384716/8ca9b3d7d891/12951_2024_2746_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a2e/11384716/88b190cea5f6/12951_2024_2746_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a2e/11384716/0ae48337146b/12951_2024_2746_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a2e/11384716/0542964e084e/12951_2024_2746_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a2e/11384716/3bb68ea4d86b/12951_2024_2746_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a2e/11384716/8ca9b3d7d891/12951_2024_2746_Fig5_HTML.jpg

相似文献

[1]
Non-viral approaches in CAR-NK cell engineering: connecting natural killer cell biology and gene delivery.

J Nanobiotechnology. 2024-9-10

[2]
Chimeric antigen receptor (CAR) natural killer (NK)-cell therapy: leveraging the power of innate immunity.

Br J Haematol. 2021-4

[3]
Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy.

J Hematol Oncol. 2020-12-7

[4]
Current Perspectives on "Off-The-Shelf" Allogeneic NK and CAR-NK Cell Therapies.

Front Immunol. 2021

[5]
Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy.

J Hematol Oncol. 2021-5-1

[6]
CAR-NK Cells: From Natural Basis to Design for Kill.

Front Immunol. 2021

[7]
Engineering the Bridge between Innate and Adaptive Immunity for Cancer Immunotherapy: Focus on γδ T and NK Cells.

Cells. 2020-7-22

[8]
Use of Cell and Genome Modification Technologies to Generate Improved "Off-the-Shelf" CAR T and CAR NK Cells.

Front Immunol. 2020

[9]
Chimeric antigen receptor-natural killer cell therapy: current advancements and strategies to overcome challenges.

Front Immunol. 2024

[10]
Engineering of potent CAR NK cells using non-viral Sleeping Beauty transposition from minimalistic DNA vectors.

Mol Ther. 2024-7-3

引用本文的文献

[1]
CAR-iNKT cells: redefining the frontiers of cellular immunotherapy.

Front Immunol. 2025-7-11

[2]
Antitumor and immunomodulatory activities of diphyllin and its derivatives.

Bioorg Med Chem. 2025-7-1

本文引用的文献

[1]
Pretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation.

Nat Commun. 2024-5-10

[2]
Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy.

Cells. 2024-3-5

[3]
Endosomal escape: A bottleneck for LNP-mediated therapeutics.

Proc Natl Acad Sci U S A. 2024-3-12

[4]
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-Thalassemia.

Med Sci Monit. 2024-3-1

[5]
Reprogramming natural killer cells for cancer therapy.

Mol Ther. 2024-9-4

[6]
Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19 B cell tumors: a phase 1/2 trial.

Nat Med. 2024-3

[7]
Lipid nanoparticle-mediated messenger RNA delivery for ex vivo engineering of natural killer cells.

J Control Release. 2023-9

[8]
Chimeric antigen receptor engineered natural killer cells for cancer therapy.

Exp Hematol Oncol. 2023-8-10

[9]
Intracranial injection of natural killer cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma.

Neuro Oncol. 2023-11-2

[10]
Efficient engineering of human and mouse primary cells using peptide-assisted genome editing.

Nat Biotechnol. 2024-2

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