• 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

颅内注射 B7-H3 靶向 Car-T 和 Car-NK 细胞在患者来源的胶质母细胞瘤异种移植模型中的抗肿瘤作用。

Antitumor effects of intracranial injection of B7-H3-targeted Car-T and Car-Nk cells in a patient-derived glioblastoma xenograft model.

机构信息

Department of Neurosurgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 5650871, Japan.

World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.

出版信息

Cancer Immunol Immunother. 2024 Oct 5;73(12):256. doi: 10.1007/s00262-024-03808-0.

DOI:10.1007/s00262-024-03808-0
PMID:39367952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11456075/
Abstract

BACKGROUND

Glioblastoma multiforme (GBM) is the most lethal primary brain tumor for which novel therapies are needed. Recently, chimeric antigen receptor (CAR) T cell therapy has been shown to be effective against GBM, but it is a personalized medicine and requires high cost and long time for the cell production. CAR-transduced natural killer (NK) cells can be used for "off-the-shelf" cellular immunotherapy because they do not induce graft-versus-host disease. Therefore, we aimed to analyze the anti-GBM effect of CAR-T or NK cells targeting B7-H3, which is known to be highly expressed in GBM.

METHODS

CAR-T cells targeting B7-H3 were generated using previously reported anti-B7-H3 scFv sequences. Cord blood (CB)-derived NK cells transduced with the B7-H3 CAR were also generated. Their anti-GBM effect was analyzed in vitro. The antitumor effect of intracranial injection of the B7-H3 CAR-T or NK cells was investigated in an in vivo xenograft model with patient-derived GBM cells.

RESULTS

Both B7-H3 CAR-T cells and CAR-NK cells exhibited marked cytotoxicity against patient-derived GBM cells in vitro. Furthermore, intracranial injection of CAR-T cells and CAR-NK cells targeting B7-H3 resulted in a significant antitumor effect against patient-derived GBM xenografts.

CONCLUSION

Not only CAR-T cells but also CB-derived CAR-NK cells targeting B7-H3 may have the potential to eliminate GBM cells.

摘要

背景

多形性胶质母细胞瘤（GBM）是最致命的原发性脑肿瘤，需要新的治疗方法。最近，嵌合抗原受体（CAR）T 细胞疗法已被证明对 GBM 有效，但它是一种个性化药物，细胞生产需要高成本和长时间。CAR 转导的自然杀伤（NK）细胞可用于“现货”细胞免疫疗法，因为它们不会引起移植物抗宿主病。因此，我们旨在分析针对 B7-H3 的 CAR-T 或 NK 细胞对 GBM 的抗作用，因为已知 B7-H3 在 GBM 中高度表达。

方法

使用先前报道的抗 B7-H3 scFv 序列生成针对 B7-H3 的 CAR-T 细胞。还生成了转导 B7-H3 CAR 的脐血（CB）衍生 NK 细胞。在体外分析了它们的抗 GBM 作用。在携带患者来源的 GBM 细胞的体内异种移植模型中研究了 B7-H3 CAR-T 或 NK 细胞颅内注射的抗肿瘤作用。

结果

B7-H3 CAR-T 细胞和 CAR-NK 细胞在体外均对患者来源的 GBM 细胞表现出明显的细胞毒性。此外，针对 B7-H3 的 CAR-T 细胞和 CAR-NK 细胞颅内注射对患者来源的 GBM 异种移植物具有显著的抗肿瘤作用。

结论

不仅 CAR-T 细胞，而且针对 B7-H3 的 CB 衍生 CAR-NK 细胞都有可能消除 GBM 细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b783/11456075/bc40efb31172/262_2024_3808_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b783/11456075/3c9171e09e2a/262_2024_3808_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b783/11456075/c515dca68351/262_2024_3808_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b783/11456075/bb2b22e3a898/262_2024_3808_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b783/11456075/bc40efb31172/262_2024_3808_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b783/11456075/3c9171e09e2a/262_2024_3808_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b783/11456075/c515dca68351/262_2024_3808_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b783/11456075/bb2b22e3a898/262_2024_3808_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b783/11456075/bc40efb31172/262_2024_3808_Fig4_HTML.jpg

相似文献

1
Antitumor effects of intracranial injection of B7-H3-targeted Car-T and Car-Nk cells in a patient-derived glioblastoma xenograft model.颅内注射 B7-H3 靶向 Car-T 和 Car-NK 细胞在患者来源的胶质母细胞瘤异种移植模型中的抗肿瘤作用。
Cancer Immunol Immunother. 2024 Oct 5;73(12):256. doi: 10.1007/s00262-024-03808-0.
2
B7-H3-redirected chimeric antigen receptor T cells target glioblastoma and neurospheres.B7-H3 重定向嵌合抗原受体 T 细胞靶向神经胶质瘤和神经球。
EBioMedicine. 2019 Sep;47:33-43. doi: 10.1016/j.ebiom.2019.08.030. Epub 2019 Aug 26.
3
CD19 CAR-expressing iPSC-derived NK cells effectively enhance migration and cytotoxicity into glioblastoma by targeting to the pericytes in tumor microenvironment.CD19 CAR 表达的 iPSC 衍生 NK 细胞通过靶向肿瘤微环境中的周细胞，有效增强了对神经胶质瘤的迁移和细胞毒性。
Biomed Pharmacother. 2024 May;174:116436. doi: 10.1016/j.biopha.2024.116436. Epub 2024 Mar 19.
4
B7-H3-Targeting Chimeric Antigen Receptors Epstein-Barr Virus-specific T Cells Provides a Tumor Agnostic Off-The-Shelf Therapy Against B7-H3-positive Solid Tumors.B7-H3 靶向嵌合抗原受体 Epstein-Barr 病毒特异性 T 细胞为 B7-H3 阳性实体瘤提供了一种肿瘤不可知的现货治疗方法。
Cancer Res Commun. 2024 Jun 4;4(6):1410-1429. doi: 10.1158/2767-9764.CRC-23-0538.
5
ErbB2/HER2-Specific NK Cells for Targeted Therapy of Glioblastoma.针对胶质母细胞瘤的靶向治疗的 ErbB2/HER2 特异性 NK 细胞。
J Natl Cancer Inst. 2015 Dec 6;108(5). doi: 10.1093/jnci/djv375. Print 2016 May.
6
CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors.嵌合抗原受体 T 细胞靶向 B7-H3，一种泛癌抗原，在针对儿科实体瘤和脑肿瘤的临床前研究中显示出强大的活性。
Clin Cancer Res. 2019 Apr 15;25(8):2560-2574. doi: 10.1158/1078-0432.CCR-18-0432. Epub 2019 Jan 17.
7
Targeting B7-H3 via chimeric antigen receptor T cells and bispecific killer cell engagers augments antitumor response of cytotoxic lymphocytes.嵌合抗原受体 T 细胞和双特异性杀伤细胞衔接子靶向 B7-H3 增强了细胞毒性淋巴细胞的抗肿瘤反应。
J Hematol Oncol. 2021 Jan 29;14(1):21. doi: 10.1186/s13045-020-01024-8.
8
An Oncolytic Virus Expressing IL15/IL15Rα Combined with Off-the-Shelf EGFR-CAR NK Cells Targets Glioblastoma.表达 IL15/IL15Rα 的溶瘤病毒联合即用型 EGFR-CAR NK 细胞靶向胶质母细胞瘤。
Cancer Res. 2021 Jul 1;81(13):3635-3648. doi: 10.1158/0008-5472.CAN-21-0035. Epub 2021 May 18.
9
Antitumor Responses in the Absence of Toxicity in Solid Tumors by Targeting B7-H3 via Chimeric Antigen Receptor T Cells.嵌合抗原受体 T 细胞靶向 B7-H3 治疗实体瘤，无毒性作用下的抗肿瘤反应。
Cancer Cell. 2019 Feb 11;35(2):221-237.e8. doi: 10.1016/j.ccell.2019.01.002.
10
Directing B7-H3 chimeric antigen receptor T cell homing through IL-8 induces potent antitumor activity against pediatric sarcoma.通过白细胞介素-8 引导 B7-H3 嵌合抗原受体 T 细胞归巢，引发针对儿科肉瘤的强大抗肿瘤活性。
J Immunother Cancer. 2024 Jul 23;12(7):e009221. doi: 10.1136/jitc-2024-009221.

引用本文的文献

1
Rendering NK Cells Antigen-Specific for the Therapy of Solid Tumours.使自然杀伤细胞对实体瘤治疗具有抗原特异性。
Int J Mol Sci. 2025 Jun 29;26(13):6290. doi: 10.3390/ijms26136290.
2
Current challenges and emerging opportunities of chimeric antigen receptor-engineered cell immunotherapy.嵌合抗原受体工程化细胞免疫疗法的当前挑战与新出现的机遇
Exp Hematol Oncol. 2025 Jul 2;14(1):92. doi: 10.1186/s40164-025-00683-y.
3
Near-Infrared Photoimmunotherapy in Brain Tumors-An Unexplored Frontier.脑肿瘤的近红外光免疫疗法——一个未被探索的前沿领域。

本文引用的文献

1
Identification of genetic modifiers enhancing B7-H3-targeting CAR T cell therapy against glioblastoma through large-scale CRISPRi screening.通过大规模 CRISPRi 筛选鉴定增强 B7-H3 靶向 CAR T 细胞治疗胶质母细胞瘤的遗传修饰物。
J Exp Clin Cancer Res. 2024 Apr 1;43(1):95. doi: 10.1186/s13046-024-03027-6.
2
Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19 B cell tumors: a phase 1/2 trial.同种异体 CD19 特异性 CAR-NK 细胞治疗 CD19 B 细胞肿瘤的安全性、有效性和反应决定因素：一项 1/2 期试验。
Nat Med. 2024 Mar;30(3):772-784. doi: 10.1038/s41591-023-02785-8. Epub 2024 Jan 18.
3
Pharmaceuticals (Basel). 2025 May 19;18(5):751. doi: 10.3390/ph18050751.
4
Tumor Treating Fields and Combination Therapy in Management of Brain Oncology.肿瘤治疗电场与联合疗法在脑肿瘤治疗中的应用
Cancers (Basel). 2025 Apr 2;17(7):1211. doi: 10.3390/cancers17071211.
5
Towards Effective Treatment of Glioblastoma: The Role of Combination Therapies and the Potential of Phytotherapy and Micotherapy.迈向胶质母细胞瘤的有效治疗：联合疗法的作用以及植物疗法和微疗法的潜力
Curr Issues Mol Biol. 2024 Dec 19;46(12):14324-14350. doi: 10.3390/cimb46120859.
Impact of tumor microenvironment on efficacy of anti-CD19 CAR T cell therapy or chemotherapy and transplant in large B cell lymphoma.
肿瘤微环境对大 B 细胞淋巴瘤中抗 CD19 CAR T 细胞治疗或化疗和移植疗效的影响。
Nat Med. 2024 Feb;30(2):507-518. doi: 10.1038/s41591-023-02754-1. Epub 2024 Jan 17.
4
Single-cell analysis reveals diversity of tumor-associated macrophages and their interactions with T lymphocytes in glioblastoma.单细胞分析揭示胶质母细胞瘤中肿瘤相关巨噬细胞的多样性及其与 T 淋巴细胞的相互作用。
Sci Rep. 2023 Nov 27;13(1):20874. doi: 10.1038/s41598-023-48116-2.
5
Therapeutic effects against high-grade glioblastoma mediated by engineered induced neural stem cells combined with GD2-specific CAR-NK.工程化诱导神经干细胞联合 GD2 特异性 CAR-NK 对高级别神经胶质瘤的治疗作用。
Cell Oncol (Dordr). 2023 Dec;46(6):1747-1762. doi: 10.1007/s13402-023-00842-5. Epub 2023 Jul 7.
6
Intracranial injection of natural killer cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma.在复发性胶质母细胞瘤患者中，经 HER2 靶向嵌合抗原受体工程化的自然杀伤细胞颅内注射。
Neuro Oncol. 2023 Nov 2;25(11):2058-2071. doi: 10.1093/neuonc/noad087.
7
Tumor microenvironment in glioblastoma: Current and emerging concepts.胶质母细胞瘤中的肿瘤微环境：当前及新出现的概念
Neurooncol Adv. 2023 Feb 23;5(1):vdad009. doi: 10.1093/noajnl/vdad009. eCollection 2023 Jan-Dec.
8
Identification of glioblastoma-specific antigens expressed in patient-derived tumor cells as candidate targets for chimeric antigen receptor T cell therapy.鉴定在患者来源的肿瘤细胞中表达的胶质母细胞瘤特异性抗原，作为嵌合抗原受体T细胞疗法的候选靶点。
Neurooncol Adv. 2022 Nov 15;5(1):vdac177. doi: 10.1093/noajnl/vdac177. eCollection 2023 Jan-Dec.
9
Allogeneic natural killer cell therapy.异体自然杀伤细胞治疗。
Blood. 2023 Feb 23;141(8):856-868. doi: 10.1182/blood.2022016200.
10
Co-transducing B7H3 CAR-NK cells with the DNR preserves their cytolytic function against GBM in the presence of exogenous TGF-β.在存在外源性转化生长因子-β（TGF-β）的情况下，用柔红霉素（DNR）共转导B7H3嵌合抗原受体自然杀伤细胞（CAR-NK细胞）可保留它们对胶质母细胞瘤（GBM）的细胞溶解功能。
Mol Ther Methods Clin Dev. 2022 Oct 21;27:415-430. doi: 10.1016/j.omtm.2022.10.010. eCollection 2022 Dec 8.