文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

临床开发中的自然杀伤细胞作为非工程化、工程化和联合疗法。

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

机构信息

Glycostem Therapeutics, Kloosterstraat 9, 5349 AB, Oss, The Netherlands.

出版信息

J Hematol Oncol. 2022 Nov 8;15(1):164. doi: 10.1186/s13045-022-01382-5.


DOI:10.1186/s13045-022-01382-5
PMID:36348457
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9644572/
Abstract

Natural killer (NK) cells are unique immune effectors able to kill cancer cells by direct recognition of surface ligands, without prior sensitization. Allogeneic NK transfer is a highly valuable treatment option for cancer and has recently emerged with hundreds of clinical trials paving the way to finally achieve market authorization. Advantages of NK cell therapies include the use of allogenic cell sources, off-the-shelf availability, and no risk of graft-versus-host disease (GvHD). Allogeneic NK cell therapies have reached the clinical stage as ex vivo expanded and differentiated non-engineered cells, as chimeric antigen receptor (CAR)-engineered or CD16-engineered products, or as combination therapies with antibodies, priming agents, and other drugs. This review summarizes the recent clinical status of allogeneic NK cell-based therapies for the treatment of hematological and solid tumors, discussing the main characteristics of the different cell sources used for NK product development, their use in cell manufacturing processes, the engineering methods and strategies adopted for genetically modified products, and the chosen approaches for combination therapies. A comparative analysis between NK-based non-engineered, engineered, and combination therapies is presented, examining the choices made by product developers regarding the NK cell source and the targeted tumor indications, for both solid and hematological cancers. Clinical trial outcomes are discussed and, when available, assessed in comparison with preclinical data. Regulatory challenges for product approval are reviewed, highlighting the lack of specificity of requirements and standardization between products. Additionally, the competitive landscape and business field is presented. This review offers a comprehensive overview of the effort driven by biotech and pharmaceutical companies and by academic centers to bring NK cell therapies to pivotal clinical trial stages and to market authorization.

摘要

自然杀伤 (NK) 细胞是独特的免疫效应细胞,能够通过直接识别表面配体杀死癌细胞,而无需预先致敏。同种异体 NK 细胞转移是一种非常有价值的癌症治疗选择,最近已有数百项临床试验为最终实现市场授权铺平了道路。NK 细胞疗法的优势包括使用同种异体细胞来源、现成可用性和无移植物抗宿主病 (GvHD) 风险。同种异体 NK 细胞疗法已经进入临床阶段,作为体外扩增和分化的非工程细胞、嵌合抗原受体 (CAR) 工程或 CD16 工程产品,或作为与抗体、启动剂和其他药物的联合疗法。本综述总结了同种异体 NK 细胞为基础的治疗血液系统和实体肿瘤的最新临床现状,讨论了用于 NK 产品开发的不同细胞来源的主要特征,其在细胞制造过程中的用途,用于基因修饰产品的工程方法和策略,以及联合疗法的选择方法。对基于 NK 的非工程、工程和联合疗法进行了比较分析,检查了产品开发人员在 NK 细胞来源和靶向肿瘤适应症方面的选择,包括血液系统和实体瘤癌症。讨论了临床试验结果,并在可用时与临床前数据进行了比较。审查了产品批准的监管挑战,强调了产品之间要求和标准化的缺乏特异性。此外,还介绍了竞争格局和商业领域。本综述全面概述了生物技术和制药公司以及学术中心为将 NK 细胞疗法推向关键临床试验阶段和市场授权所做的努力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/c2d486712b81/13045_2022_1382_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/52ff1381cd4c/13045_2022_1382_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/a502f70c6cf3/13045_2022_1382_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/92482ee67268/13045_2022_1382_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/ce9c0ef3e91c/13045_2022_1382_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/14ecd20b6e24/13045_2022_1382_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/2c20b2db63d3/13045_2022_1382_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/c2d486712b81/13045_2022_1382_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/52ff1381cd4c/13045_2022_1382_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/a502f70c6cf3/13045_2022_1382_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/92482ee67268/13045_2022_1382_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/ce9c0ef3e91c/13045_2022_1382_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/14ecd20b6e24/13045_2022_1382_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/2c20b2db63d3/13045_2022_1382_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2366/9644572/c2d486712b81/13045_2022_1382_Fig7_HTML.jpg

相似文献

[1]
Natural killer cells in clinical development as non-engineered, engineered, and combination therapies.

J Hematol Oncol. 2022-11-8

[2]
Antitumor activity of genetically engineered NK-cells in non-hematological solid tumor: a comprehensive review.

Front Immunol. 2024

[3]
CAR-NK Cells: From Natural Basis to Design for Kill.

Front Immunol. 2021

[4]
Chimeric antigen receptor (CAR) natural killer (NK)-cell therapy: leveraging the power of innate immunity.

Br J Haematol. 2021-4

[5]
[Allogeneic CAR-NK cells: A promising alternative to autologous CAR-T cells - State of the art, sources of NK cells, limits and perspectives].

Bull Cancer. 2021-10

[6]
CAR-engineered NK cells; a promising therapeutic option for treatment of hematological malignancies.

Stem Cell Res Ther. 2021-7-2

[7]
Current Perspectives on "Off-The-Shelf" Allogeneic NK and CAR-NK Cell Therapies.

Front Immunol. 2021

[8]
Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of Cancer.

Front Immunol. 2018-2-15

[9]
Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy.

J Hematol Oncol. 2020-12-7

[10]
Charting a killer course to the solid tumor: strategies to recruit and activate NK cells in the tumor microenvironment.

Front Immunol. 2023

引用本文的文献

[1]
A Type I IFN-Inducing Oncolytic Virus Improves NK Cell-Mediated Killing of Tumor Cells In Vitro Through Multiple Mechanisms.

Viruses. 2025-6-25

[2]
Stem Cell for Cancer Immunotherapy: Current Approaches and Challenges.

Stem Cell Rev Rep. 2025-10

[3]
Closed-system manufacturing of therapeutic NK cells using automated cell enrichment and concentration processes enables scalable, robust and cost-effective solutions.

Front Bioeng Biotechnol. 2025-6-25

[4]
Oncolytic adeno-immunotherapy improves allogeneic adoptive HER2.CAR-NK function against pancreatic ductal adenocarcinoma.

Mol Ther Oncol. 2025-5-26

[5]
CAR-NK, a Splendid Strategy for Cancer, Especially for Gynecologic Tumor.

Immun Inflamm Dis. 2025-6

[6]
CD28 signaling domain boosts persistence and anti-tumor activity of stem cell-derived CD19-CAR-NK cells.

iScience. 2025-4-29

[7]
Application and prospects of genetic engineering in CAR-NK cell therapy.

Front Immunol. 2025-5-23

[8]
Good manufacturing practice production of an off-the-shelf CD34 progenitor-derived NK cell product with preserved anti-tumor functionality post-infusion in NOD/SCID/IL2Rg mice.

Cell Mol Life Sci. 2025-5-26

[9]
Targeting ATF5, CEBPB, and CEBPD with Cell-Penetrating Dpep Sensitizes Tumor Cells to NK-92MI Cell Cytotoxicity.

Cells. 2025-5-2

[10]
In Vitro Expansion and Transduction of Primary NK Cells Using Feeder Cells Expressing Costimulatory Molecules and IL-21.

Cancer Sci. 2025-7

本文引用的文献

[1]
Natural killer cells in antitumour adoptive cell immunotherapy.

Nat Rev Cancer. 2022-10

[2]
Engineering Induced Pluripotent Stem Cells for Cancer Immunotherapy.

Cancers (Basel). 2022-5-1

[3]
Regulatory Considerations for Clinical Trial Applications with CRISPR-Based Medicinal Products.

CRISPR J. 2022-6

[4]
Human placental hematopoietic stem cell derived natural killer cells (CYNK-001) mediate protection against influenza a viral infection.

Hum Vaccin Immunother. 2022-11-30

[5]
Innovative Strategies to Improve the Clinical Application of NK Cell-Based Immunotherapy.

Front Immunol. 2022

[6]
Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell Killing.

Cells. 2021-12-22

[7]
Current Perspectives on "Off-The-Shelf" Allogeneic NK and CAR-NK Cell Therapies.

Front Immunol. 2021

[8]
Genetically engineered CAR T-immune cells for cancer therapy: recent clinical developments, challenges, and future directions.

J Appl Biomed. 2019-3

[9]
Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A.

J Clin Oncol. 2022-2-1

[10]
piggyBac system to co-express NKG2D CAR and IL-15 to augment the persistence and anti-AML activity of human peripheral blood NK cells.

Mol Ther Methods Clin Dev. 2021-11-4

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索