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使自然杀伤细胞对实体瘤治疗具有抗原特异性。

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

作者信息

Doeppner Carina A, Binder Amanda Katharina, Bremm Franziska, Feuchter Niklas, Dörrie Jan, Schaft Niels

机构信息

Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.

Comprehensive Cancer Center Erlangen European Metropolitan Area of Nuremberg (CCC ER-EMN), 91054 Erlangen, Germany.

出版信息

Int J Mol Sci. 2025 Jun 29;26(13):6290. doi: 10.3390/ijms26136290.


DOI:10.3390/ijms26136290
PMID:40650066
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12249712/
Abstract

Cancer remains one of the leading causes of death worldwide. New treatments like immunotherapy-especially checkpoint inhibitors and CAR-T cell therapy-have improved outcomes for some patients. However, these therapies often struggle to treat solid tumours effectively. Natural killer (NK) cells are part of the immune system and can naturally detect and destroy cancer cells without previous adaption. Scientists are now enhancing these cells by adding special receptors, called CARs (chimeric antigen receptors), to help them better recognize and attack cancer, an approach originally developed for T cells. CAR-NK cell therapy has some advantages over CAR-T therapy. It tends to cause fewer severe side effects, such as strong immune reactions or off-target effects in healthy tissues. Within some limitations, the allogenic use of CAR-NK cells is possible, as these cells exert less graft-versus-host activity. Such CAR-NK cell products can be produced in larger quantities and stored, making treatment more accessible. Still, there are challenges. It can be difficult to create enough modified NK cells, and the tumour microenvironment can block their activity. This review highlights recent progress in CAR-NK therapy, including early lab and clinical research. It also explores ways to improve these treatments and how they might work alongside other cancer therapies to help more patients in the future.

摘要

癌症仍然是全球主要死因之一。免疫疗法等新疗法——尤其是检查点抑制剂和嵌合抗原受体T细胞(CAR-T)疗法——改善了部分患者的治疗效果。然而,这些疗法往往难以有效治疗实体瘤。自然杀伤(NK)细胞是免疫系统的一部分,能够在无需预先适应的情况下自然检测并摧毁癌细胞。科学家们现在通过添加名为嵌合抗原受体(CAR)的特殊受体来增强这些细胞,以帮助它们更好地识别和攻击癌症,这一方法最初是为T细胞开发的。CAR-NK细胞疗法相对于CAR-T疗法具有一些优势。它往往会引发较少的严重副作用,如强烈的免疫反应或健康组织中的脱靶效应。在某些限制条件下,CAR-NK细胞的同种异体使用是可行的,因为这些细胞产生的移植物抗宿主活性较小。此类CAR-NK细胞产品可以大量生产和储存,使治疗更容易获得。不过,仍然存在挑战。难以制造出足够数量的经过改造的NK细胞,而且肿瘤微环境会阻碍它们的活性。这篇综述重点介绍了CAR-NK疗法的最新进展,包括早期的实验室研究和临床研究。它还探讨了改进这些治疗方法的途径,以及它们未来如何与其他癌症疗法协同作用以帮助更多患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c273/12249712/d9e553ca9b4b/ijms-26-06290-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c273/12249712/165162bf2093/ijms-26-06290-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c273/12249712/7851b2293adf/ijms-26-06290-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c273/12249712/d9e553ca9b4b/ijms-26-06290-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c273/12249712/165162bf2093/ijms-26-06290-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c273/12249712/7851b2293adf/ijms-26-06290-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c273/12249712/d9e553ca9b4b/ijms-26-06290-g003.jpg

相似文献

[1]
Rendering NK Cells Antigen-Specific for the Therapy of Solid Tumours.

Int J Mol Sci. 2025-6-29

[2]
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[3]
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[4]
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[6]
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[7]
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[8]
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[9]
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Drug Saf. 2025-3-19

[10]
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Immunotherapy. 2025-2

本文引用的文献

[1]
CAR-NK cells with dual targeting of PD-L1 and MICA/B in lung cancer tumor models.

BMC Cancer. 2025-2-25

[2]
Combinatorial immunotherapy with anti-ROR1 CAR NK cells and an IL-21 secreting oncolytic virus against neuroblastoma.

Mol Ther Oncol. 2024-12-21

[3]
Chimeric cytokine receptor TGF-β RⅡ/IL-21R improves CAR-NK cell function by reversing the immunosuppressive tumor microenvironment of gastric cancer.

Pharmacol Res. 2025-2

[4]
Exploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma.

PLoS One. 2025-1-22

[5]
Virus-free CRISPR knockin of a chimeric antigen receptor into KLRC1 generates potent GD2-specific natural killer cells.

Mol Ther. 2025-3-5

[6]
Enhancement of anti-sarcoma immunity by NK cells engineered with mRNA for expression of a EphA2-targeted CAR.

Clin Transl Med. 2025-1

[7]
Peptide-based CAR-NK cells: A novel strategy for the treatment of solid tumors.

Biochem Pharmacol. 2025-2

[8]
Therapeutic potential of anti-ErbB3 chimeric antigen receptor natural killer cells against breast cancer.

Cancer Immunol Immunother. 2025-1-3

[9]
Artificial intelligence for chimeric antigen receptor-based therapies: a comprehensive review of current applications and future perspectives.

Ther Adv Vaccines Immunother. 2024-12-16

[10]
A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?

Front Immunol. 2024

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