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嵌合抗原受体自然杀伤细胞免疫疗法治疗癌症:从基础到临床。

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

机构信息

Institute of Biomedical Research, Yunnan University, Kunming, 650500, China.

Graduate School of Capital Medical University, Beijing, 100069, China.

出版信息

Cell Death Dis. 2024 Jan 15;15(1):50. doi: 10.1038/s41419-024-06438-7.


DOI:10.1038/s41419-024-06438-7
PMID:38221520
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10788349/
Abstract

Immunotherapy has rapidly evolved in the past decades in the battle against cancer. Chimeric antigen receptor (CAR)-engineered T cells have demonstrated significant success in certain hematologic malignancies, although they still face certain limitations, including high costs and toxic effects. Natural killer cells (NK cells), as a vital component of the immune system, serve as the "first responders" in the context of cancer development. In this literature review, we provide an updated understanding of NK cell development, functions, and their applications in disease therapy. Furthermore, we explore the rationale for utilizing engineered NK cell therapies, such as CAR-NK cells, and discuss the differences between CAR-T and CAR-NK cells. We also provide insights into the key elements and strategies involved in CAR design for engineered NK cells. In addition, we highlight the challenges currently encountered and discuss the future directions in NK cell research and utilization, including pre-clinical investigations and ongoing clinical trials. Based on the outstanding antitumor potential of NK cells, it is highly likely that they will lead to groundbreaking advancements in cancer treatment in the future.

摘要

免疫疗法在过去几十年中在抗击癌症的斗争中迅速发展。嵌合抗原受体 (CAR)-修饰的 T 细胞在某些血液恶性肿瘤中已经显示出显著的成功,尽管它们仍然面临一些限制,包括高成本和毒性作用。自然杀伤细胞 (NK 细胞) 作为免疫系统的重要组成部分,在癌症发展中充当“第一反应者”。在这篇文献综述中,我们提供了对 NK 细胞发育、功能及其在疾病治疗中的应用的最新认识。此外,我们探讨了利用工程化 NK 细胞疗法(如 CAR-NK 细胞)的原理,并讨论了 CAR-T 和 CAR-NK 细胞之间的差异。我们还介绍了 CAR 设计中涉及的关键要素和策略。此外,我们强调了当前遇到的挑战,并讨论了 NK 细胞研究和应用的未来方向,包括临床前研究和正在进行的临床试验。基于 NK 细胞出色的抗肿瘤潜力,它们很有可能在未来引领癌症治疗的突破性进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/669ab72deeaf/41419_2024_6438_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/33c46dec9c5f/41419_2024_6438_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/b630a1c34e22/41419_2024_6438_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/8031c2f7aaf0/41419_2024_6438_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/d91690bcc11c/41419_2024_6438_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/0a724da05bb2/41419_2024_6438_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/0d23900966ac/41419_2024_6438_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/e0041fba9fc1/41419_2024_6438_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/669ab72deeaf/41419_2024_6438_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/33c46dec9c5f/41419_2024_6438_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/b630a1c34e22/41419_2024_6438_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/8031c2f7aaf0/41419_2024_6438_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/d91690bcc11c/41419_2024_6438_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/0a724da05bb2/41419_2024_6438_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/0d23900966ac/41419_2024_6438_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/e0041fba9fc1/41419_2024_6438_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5337/10788349/669ab72deeaf/41419_2024_6438_Fig8_HTML.jpg

相似文献

[1]
Chimeric antigen receptor-based natural killer cell immunotherapy in cancer: from bench to bedside.

Cell Death Dis. 2024-1-15

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

Br J Haematol. 2021-4

[3]
Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy.

Front Immunol. 2023

[4]
CAR-NK Cells: From Natural Basis to Design for Kill.

Front Immunol. 2021

[5]
Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy.

J Hematol Oncol. 2020-12-7

[6]
Current progress of chimeric antigen receptor (CAR) T versus CAR NK cell for immunotherapy of solid tumors.

Life Sci. 2024-1-15

[7]
Engineering chimeric antigen receptor-natural killer cells for cancer immunotherapy.

Immunotherapy. 2020-6

[8]
Chimeric antigen receptor-natural killer cell therapy: current advancements and strategies to overcome challenges.

Front Immunol. 2024

[9]
Reformation in chimeric antigen receptor based cancer immunotherapy: Redirecting natural killer cell.

Biochim Biophys Acta Rev Cancer. 2018-1-31

[10]
The Next Generation of Cellular Immunotherapy: Chimeric Antigen Receptor-Natural Killer Cells.

Transplant Cell Ther. 2022-10

引用本文的文献

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

Int J Mol Sci. 2025-6-29

[2]
Schottky barrier in pea-like Au@BiS nanoreactor enabling efficient photodynamic therapy of hepatocellular carcinoma.

Mater Today Bio. 2025-6-19

[3]
Optimization of lentiviral delivery of barcoded anti-CD20 chimeric antigen receptors into rhesus macaque and human natural killer cells.

Mol Ther Methods Clin Dev. 2025-4-18

[4]
Chimeric Antigen Receptor T-cell therapy in systemic autoimmune rheumatic diseases: current insights and future prospects.

J Rheum Dis. 2025-7-1

[5]
Application and prospects of genetic engineering in CAR-NK cell therapy.

Front Immunol. 2025-5-23

[6]
Emerging Role of Chimeric Antigen Receptor-Natural Killer Cells for the Treatment of Hematologic Malignancies.

Cancers (Basel). 2025-4-26

[7]
The Role of NK Cells in Cancer Immunotherapy: Mechanisms, Evasion Strategies, and Therapeutic Advances.

Biomedicines. 2025-4-2

[8]
CAR-NK cell therapy: promise and challenges in solid tumors.

Front Immunol. 2025-4-7

[9]
Engineering innate immune cells for cancer immunotherapy.

Nat Biotechnol. 2025-4

[10]
Novel gene manipulation approaches to unlock the existing bottlenecks of CAR-NK cell therapy.

Front Cell Dev Biol. 2025-2-11

本文引用的文献

[1]
Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy.

Front Immunol. 2023

[2]
Engaging natural killer cells for cancer therapy via NKG2D, CD16A and other receptors.

MAbs. 2023

[3]
A highly efficient transgene knock-in technology in clinically relevant cell types.

Nat Biotechnol. 2024-3

[4]
Adapter CAR T cells to counteract T-cell exhaustion and enable flexible targeting in AML.

Leukemia. 2023-6

[5]
Engineering a HER2-CAR-NK Cell Secreting Soluble Programmed Cell Death Protein with Superior Antitumor Efficacy.

Int J Mol Sci. 2023-4-6

[6]
CAR-NK cell therapy for hematological malignancies: recent updates from ASH 2022.

J Hematol Oncol. 2023-4-7

[7]
Heterodimeric IL-15 (hetIL-15) reduces circulating tumor cells and metastasis formation improving chemotherapy and surgery in 4T1 mouse model of TNBC.

Front Immunol. 2022

[8]
Natural killer cells and type 1 innate lymphoid cells in cancer.

Semin Immunol. 2023-3

[9]
Natural killer cells in clinical development as non-engineered, engineered, and combination therapies.

J Hematol Oncol. 2022-11-8

[10]
Safe and effective off-the-shelf immunotherapy based on CAR.CD123-NK cells for the treatment of acute myeloid leukaemia.

J Hematol Oncol. 2022-11-5

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