• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
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
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
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 @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

无饲养层培养方案扩增的外周血单个核细胞来源的自然杀伤细胞对卵巢癌的抗肿瘤活性

Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer.

作者信息

Chen Minhua, Li Yutong, Wu Yu, Xie Siqi, Ma Jie, Yue Jingjing, Lv Rong, Tian Zhigang, Fang Fang, Xiao Weihua

机构信息

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.

Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.

出版信息

Cancers (Basel). 2021 Nov 22;13(22):5866. doi: 10.3390/cancers13225866.

DOI:10.3390/cancers13225866
PMID:34831019
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8616155/
Abstract

Natural killer (NK) cells have shown great therapeutic potential against a wide range of cancers due to their pan-specific target recognition. Numerous reports indicate that NK cell immunotherapy is an effective therapeutic approach for treating hematological malignancies, but shows limited effects against solid tumors. In this study, several models of ovarian cancer (OC) were used to test the anti-cancer effects of NK cells derived from human peripheral blood mononuclear cells and expanded using a feeder cell-free expansion system (eNKs). The results show that eNKs exhibit potent inhibitory activity on tumor growth in different ovarian cancer xenograft mice (i.e., solid tumors, abdominal metastatic tumors, and ascites), importantly, in a dose-dependent manner. Moreover, adoptive transfer of eNKs resulted in significant reduction in ascites formation in OC peritoneal tumor models, and especially in reducing intraperitoneal ascites. We found that eNKs could migrate to the tumor site, retain their activity, and proliferate to maintain high cell counts in cutaneous xenograft mice. In addition, when increased the infusion with a high dose of 12 × 10 cells/mouse, Graft-versus-host disease could be induced by eNK. These data show that eNK cell immunotherapy could be a promising treatment strategy for ovarian cancers, including solid tumors and ascites.

摘要

自然杀伤(NK)细胞因其泛特异性的靶标识别能力,在多种癌症的治疗中展现出巨大的治疗潜力。众多报告表明,NK细胞免疫疗法是治疗血液系统恶性肿瘤的有效治疗方法,但对实体瘤的疗效有限。在本研究中,使用了几种卵巢癌(OC)模型来测试源自人外周血单个核细胞并通过无饲养细胞扩增系统(eNKs)扩增的NK细胞的抗癌效果。结果表明,eNKs对不同卵巢癌异种移植小鼠(即实体瘤、腹部转移瘤和腹水)的肿瘤生长表现出强大的抑制活性,重要的是,呈剂量依赖性。此外,过继转移eNKs可显著减少OC腹膜肿瘤模型中腹水的形成,尤其是减少腹腔内腹水。我们发现,eNKs能够迁移至肿瘤部位,保持其活性,并在皮肤异种移植小鼠中增殖以维持高细胞计数。此外,当以12×10个细胞/小鼠的高剂量增加输注量时,eNK可诱导移植物抗宿主病。这些数据表明,eNK细胞免疫疗法可能是治疗卵巢癌(包括实体瘤和腹水)的一种有前景的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/cd6a18c9459f/cancers-13-05866-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/1f58d73eefd6/cancers-13-05866-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/6d1252080260/cancers-13-05866-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/f22d4f1a0e29/cancers-13-05866-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/ae86aa32f342/cancers-13-05866-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/356030c36782/cancers-13-05866-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/8447b495d975/cancers-13-05866-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/cd6a18c9459f/cancers-13-05866-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/1f58d73eefd6/cancers-13-05866-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/6d1252080260/cancers-13-05866-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/f22d4f1a0e29/cancers-13-05866-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/ae86aa32f342/cancers-13-05866-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/356030c36782/cancers-13-05866-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/8447b495d975/cancers-13-05866-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d02/8616155/cd6a18c9459f/cancers-13-05866-g007.jpg

相似文献

1
Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer.无饲养层培养方案扩增的外周血单个核细胞来源的自然杀伤细胞对卵巢癌的抗肿瘤活性
Cancers (Basel). 2021 Nov 22;13(22):5866. doi: 10.3390/cancers13225866.
2
Ex vivo-expanded NK cells from blood and ascites of ovarian cancer patients are cytotoxic against autologous primary ovarian cancer cells.从卵巢癌患者的血液和腹水中扩增的 NK 细胞对自体原发性卵巢癌细胞具有细胞毒性。
Cancer Immunol Immunother. 2018 Apr;67(4):575-587. doi: 10.1007/s00262-017-2112-x. Epub 2018 Jan 3.
3
Expanded CD56CD16 NK Cells from Ovarian Cancer Patients Are Cytotoxic against Autologous Tumor in a Patient-Derived Xenograft Murine Model.卵巢癌患者来源的扩增 CD56CD16 NK 细胞在患者来源异种移植小鼠模型中对自体肿瘤具有细胞毒性。
Cancer Immunol Res. 2018 Oct;6(10):1174-1185. doi: 10.1158/2326-6066.CIR-18-0144. Epub 2018 Jul 17.
4
Expanded natural killer cells augment the antimyeloma effect of daratumumab, bortezomib, and dexamethasone in a mouse model.扩增的自然杀伤细胞增强了达雷妥尤单抗、硼替佐米和地塞米松在小鼠模型中的抗骨髓瘤作用。
Cell Mol Immunol. 2021 Jul;18(7):1652-1661. doi: 10.1038/s41423-021-00686-9. Epub 2021 May 12.
5
Expanded natural killer cells potentiate the antimyeloma activity of daratumumab, lenalidomide, and dexamethasone in a myeloma xenograft model.扩增的自然杀伤细胞增强了达雷妥尤单抗、来那度胺和地塞米松在骨髓瘤异种移植模型中的抗骨髓瘤活性。
Cancer Immunol Immunother. 2023 May;72(5):1233-1246. doi: 10.1007/s00262-022-03322-1. Epub 2022 Nov 16.
6
Expanded NK cells from umbilical cord blood and adult peripheral blood combined with daratumumab are effective against tumor cells from multiple myeloma patients.来自脐带血和成人外周血的扩增自然杀伤细胞(NK细胞)与达雷妥尤单抗联合使用,对多发性骨髓瘤患者的肿瘤细胞有效。
Oncoimmunology. 2020 Dec 29;10(1):1853314. doi: 10.1080/2162402X.2020.1853314.
7
Cytokine-induced memory-like natural killer cells have enhanced function, proliferation, and in vivo expansion against ovarian cancer cells.细胞因子诱导的记忆样自然杀伤细胞具有增强的功能、增殖能力,并在体内扩增以对抗卵巢癌细胞。
Gynecol Oncol. 2019 Apr;153(1):149-157. doi: 10.1016/j.ygyno.2019.01.006. Epub 2019 Jan 15.
8
Autologous Immune Enhancement Therapy for Cancer - Our experience since 2004.癌症自体免疫增强疗法——我们自2004年以来的经验
J Stem Cells Regen Med. 2012 Nov 26;8(3):205-6. eCollection 2012.
9
IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer.白细胞介素-15超激动剂(ALT-803)增强自然杀伤(NK)细胞对卵巢癌的功能。
Gynecol Oncol. 2017 Jun;145(3):453-461. doi: 10.1016/j.ygyno.2017.02.028. Epub 2017 Feb 22.
10
Natural Killer Cell Expansion with Autologous Feeder Layer and Anti-CD3 Antibody for Immune Cell Therapy of Hepatocellular Carcinoma.利用自体饲养层和抗CD3抗体扩增自然杀伤细胞用于肝细胞癌的免疫细胞治疗
Asian Pac J Cancer Prev. 2019 Dec 1;20(12):3797-3803. doi: 10.31557/APJCP.2019.20.12.3797.

引用本文的文献

1
The mouse resource at National Resource Center for Mutant Mice of China.中国国家实验动物种子中心的小鼠资源。
Mamm Genome. 2025 Mar 27. doi: 10.1007/s00335-025-10118-y.
2
Potential treatment approaches for malignant peritoneal mesothelioma: in vivo and in vitro experimental study of natural killer cell immunotherapy.恶性腹膜间皮瘤的潜在治疗方法:自然杀伤细胞免疫疗法的体内和体外实验研究
Cancer Biol Med. 2024 Nov 1;21(11):1078-94. doi: 10.20892/j.issn.2095-3941.2024.0218.
3
Promising approach for targeting ROBO1 with CAR NK cells to combat ovarian cancer primary tumor cells and organoids.

本文引用的文献

1
Resistance to natural killer cell immunosurveillance confers a selective advantage to polyclonal metastasis.对自然杀伤细胞免疫监视的抗性赋予多克隆转移选择性优势。
Nat Cancer. 2020 Jul;1(7):709-722. doi: 10.1038/s43018-020-0068-9. Epub 2020 Jun 1.
2
Expanded natural killer cells augment the antimyeloma effect of daratumumab, bortezomib, and dexamethasone in a mouse model.扩增的自然杀伤细胞增强了达雷妥尤单抗、硼替佐米和地塞米松在小鼠模型中的抗骨髓瘤作用。
Cell Mol Immunol. 2021 Jul;18(7):1652-1661. doi: 10.1038/s41423-021-00686-9. Epub 2021 May 12.
3
Immunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy.
用嵌合抗原受体自然杀伤细胞(CAR NK细胞)靶向ROBO1以对抗卵巢癌原发肿瘤细胞和类器官的有前景的方法。
Future Sci OA. 2024 Jul 11;10(1):2340186. doi: 10.2144/fsoa-2023-0135. Epub 2024 Jul 29.
4
Redirect Tropism of Fowl Adenovirus 4 Vector by Modifying Fiber2 with Variable Domain of Heavy-Chain Antibody.通过用重链抗体可变域修饰纤维2来改变禽腺病毒4型载体的趋向性
Genes (Basel). 2024 Apr 8;15(4):467. doi: 10.3390/genes15040467.
5
Enhancing the therapeutic efficacy of NK cells in the treatment of ovarian cancer (Review).增强 NK 细胞在卵巢癌治疗中的疗效(综述)。
Oncol Rep. 2024 Mar;51(3). doi: 10.3892/or.2024.8709. Epub 2024 Feb 1.
6
Sufficiently activated mature natural killer cells derived from peripheral blood mononuclear cells substantially enhance antitumor activity.从外周血单核细胞中获得的充分激活的成熟自然杀伤细胞可显著增强抗肿瘤活性。
Immun Inflamm Dis. 2024 Jan;12(1):e1143. doi: 10.1002/iid3.1143.
7
Natural killer cells modified with a Gpc3 aptamer enhance adoptive immunotherapy for hepatocellular carcinoma.用Gpc3适配体修饰的自然杀伤细胞增强了对肝细胞癌的过继性免疫治疗。
Discov Oncol. 2023 Sep 4;14(1):164. doi: 10.1007/s12672-023-00780-6.
8
Murine models to study human NK cells in human solid tumors.研究人类 NK 细胞在人类实体瘤中作用的鼠类模型。
Front Immunol. 2023 Jun 14;14:1209237. doi: 10.3389/fimmu.2023.1209237. eCollection 2023.
9
Combinatorial immunotherapy with gemcitabine and ex vivo-expanded NK cells induces anti-tumor effects in pancreatic cancer.吉西他滨联合体外扩增 NK 细胞的组合免疫疗法可诱导胰腺癌产生抗肿瘤作用。
Sci Rep. 2023 May 11;13(1):7656. doi: 10.1038/s41598-023-34827-z.
10
Development of an antibody-ligand fusion protein scFvCD16Asc4-1BBL in Komagataella phaffii with stimulatory activity for Natural Killer cells.在毕赤酵母中开发具有刺激自然杀伤细胞活性的抗体-配体融合蛋白 scFvCD16Asc4-1BBL。
Microb Cell Fact. 2023 Apr 11;22(1):67. doi: 10.1186/s12934-023-02082-6.
免疫调节纳米适体增强基于抗体的癌症免疫疗法。
Nat Commun. 2021 Mar 1;12(1):1359. doi: 10.1038/s41467-021-21497-6.
4
Chemokine networks modulating natural killer cell trafficking to solid tumors.趋化因子网络调节自然杀伤细胞向实体瘤的迁移。
Cytokine Growth Factor Rev. 2021 Jun;59:36-45. doi: 10.1016/j.cytogfr.2020.12.003. Epub 2021 Jan 16.
5
NK cell-based cancer immunotherapy: from basic biology to clinical development.基于自然杀伤细胞的癌症免疫疗法:从基础生物学到临床开发。
J Hematol Oncol. 2021 Jan 6;14(1):7. doi: 10.1186/s13045-020-01014-w.
6
Design and Implementation of NK Cell-Based Immunotherapy to Overcome the Solid Tumor Microenvironment.基于自然杀伤细胞的免疫疗法设计与实施以克服实体瘤微环境
Cancers (Basel). 2020 Dec 21;12(12):3871. doi: 10.3390/cancers12123871.
7
Targeting a cytokine checkpoint enhances the fitness of armored cord blood CAR-NK cells.靶向细胞因子检查点增强了装甲脐血 CAR-NK 细胞的适应性。
Blood. 2021 Feb 4;137(5):624-636. doi: 10.1182/blood.2020007748.
8
Artificial feeder cells expressing ligands for killer cell immunoglobulin-like receptors and CD94/NKG2A for expansion of functional primary natural killer cells with tolerance to self.表达杀伤细胞免疫球蛋白样受体和 CD94/NKG2A 配体的人工饲养细胞用于扩增具有自我耐受功能的功能性原代自然杀伤细胞。
Cytotherapy. 2020 Jul;22(7):354-368. doi: 10.1016/j.jcyt.2020.02.004. Epub 2020 May 23.
9
The untapped potential of ascites in ovarian cancer research and treatment.腹水在卵巢癌研究和治疗中的未开发潜力。
Br J Cancer. 2020 Jul;123(1):9-16. doi: 10.1038/s41416-020-0875-x. Epub 2020 May 8.
10
Harnessing natural killer cells for the treatment of ovarian cancer.利用自然杀伤细胞治疗卵巢癌。
Gynecol Oncol. 2020 Jun;157(3):810-816. doi: 10.1016/j.ygyno.2020.03.020. Epub 2020 Apr 5.