• 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

双特异性抗体:设计、治疗与前景

Bispecific antibodies: design, therapy, perspectives.

作者信息

Sedykh Sergey E, Prinz Victor V, Buneva Valentina N, Nevinsky Georgy A

机构信息

Laboratory of Repair Enzymes, Siberian Branch of Russian Academy of Sciences Institute of Chemical Biology and Fundamental Medicine, Novosibirsk State University, Novosibirsk, Russia.

出版信息

Drug Des Devel Ther. 2018 Jan 22;12:195-208. doi: 10.2147/DDDT.S151282. eCollection 2018.

DOI:10.2147/DDDT.S151282
PMID:29403265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5784585/
Abstract

Antibodies (Abs) containing two different antigen-binding sites in one molecule are called bispecific. Bispecific Abs (BsAbs) were first described in the 1960s, the first monoclonal BsAbs were generated in the 1980s by hybridoma technology, and the first article describing the therapeutic use of BsAbs was published in 1992, but the number of papers devoted to BsAbs has increased significantly in the last 10 years. Particular interest in BsAbs is due to their therapeutic use. In the last decade, two BsAbs - catumaxomab in 2009 and blinatumomab in 2014, were approved for therapeutic use. Papers published in recent years have been devoted to various methods of BsAb generation by genetic engineering and chemical conjugation, and describe preclinical and clinical trials of these drugs in a variety of diseases. This review considers diverse BsAb-production methods, describes features of therapeutic BsAbs approved for medical use, and summarizes the prospects of practical application of promising new BsAbs.

摘要

在一个分子中含有两个不同抗原结合位点的抗体(Abs)被称为双特异性抗体。双特异性抗体(BsAbs)最早在20世纪60年代被描述,首批单克隆双特异性抗体于20世纪80年代通过杂交瘤技术产生,第一篇描述双特异性抗体治疗用途的文章于1992年发表,但在过去10年中,致力于双特异性抗体的论文数量显著增加。对双特异性抗体的特别关注源于其治疗用途。在过去十年中,两种双特异性抗体——2009年的卡妥索单抗和2014年的贝林妥欧单抗被批准用于治疗。近年来发表的论文致力于通过基因工程和化学偶联产生双特异性抗体的各种方法,并描述了这些药物在多种疾病中的临床前和临床试验。本综述考虑了多种双特异性抗体制备方法,描述了已批准用于医学用途的治疗性双特异性抗体的特点,并总结了有前景的新型双特异性抗体的实际应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2689/5784585/0dc7a5e3e233/dddt-12-195Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2689/5784585/b63f997e5874/dddt-12-195Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2689/5784585/c934117c6af1/dddt-12-195Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2689/5784585/0dc7a5e3e233/dddt-12-195Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2689/5784585/b63f997e5874/dddt-12-195Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2689/5784585/c934117c6af1/dddt-12-195Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2689/5784585/0dc7a5e3e233/dddt-12-195Fig3.jpg

相似文献

1
Bispecific antibodies: design, therapy, perspectives.双特异性抗体:设计、治疗与前景
Drug Des Devel Ther. 2018 Jan 22;12:195-208. doi: 10.2147/DDDT.S151282. eCollection 2018.
2
[Recent advances in the development of bispecific antibodies].[双特异性抗体研发的最新进展]
Sheng Wu Gong Cheng Xue Bao. 2020 Jan 25;36(1):33-43. doi: 10.13345/j.cjb.190154.
3
Anti-tumor activity of stability-engineered IgG-like bispecific antibodies targeting TRAIL-R2 and LTbetaR.靶向 TRAIL-R2 和 LTβR 的稳定改造 IgG 样双特异性抗体的抗肿瘤活性。
MAbs. 2009 Mar-Apr;1(2):128-41. doi: 10.4161/mabs.1.2.7631. Epub 2009 Mar 11.
4
Bispecific antibodies for cancer therapy: A review.双特异性抗体在癌症治疗中的应用:综述。
Pharmacol Ther. 2018 May;185:122-134. doi: 10.1016/j.pharmthera.2017.12.002. Epub 2017 Dec 18.
5
A pivotal decade for bispecific antibodies?双特异性抗体的关键十年?
MAbs. 2024 Jan-Dec;16(1):2321635. doi: 10.1080/19420862.2024.2321635. Epub 2024 Mar 11.
6
Bispecific monoclonal antibodies for targeted immunotherapy of solid tumors: Recent advances and clinical trials.双特异性单克隆抗体用于实体瘤的靶向免疫治疗:最新进展和临床试验。
Int J Biol Macromol. 2021 Jan 15;167:1030-1047. doi: 10.1016/j.ijbiomac.2020.11.058. Epub 2020 Nov 14.
7
Bispecific antibodies in haematological malignancies.双特异性抗体在血液恶性肿瘤中的应用。
Cancer Treat Rev. 2018 Apr;65:87-95. doi: 10.1016/j.ctrv.2018.04.002. Epub 2018 Apr 4.
8
A review of bispecific antibodies and antibody constructs in oncology and clinical challenges.双特异性抗体及抗体构建物在肿瘤学中的综述及临床挑战
Pharmacol Ther. 2019 Sep;201:103-119. doi: 10.1016/j.pharmthera.2019.04.006. Epub 2019 Apr 24.
9
Bispecific antibodies and trispecific immunocytokines for targeting the immune system against cancer: preparing for the future.双特异性抗体和三特异性免疫细胞因子靶向免疫系统治疗癌症:为未来做准备。
BioDrugs. 2013 Feb;27(1):35-53. doi: 10.1007/s40259-012-0008-z.
10
Bispecific Antibodies: From Research to Clinical Application.双特异性抗体:从研究到临床应用。
Front Immunol. 2021 May 5;12:626616. doi: 10.3389/fimmu.2021.626616. eCollection 2021.

引用本文的文献

1
Phenotypic and targeted drug discovery in immune therapeutics: challenges, opportunities, and future directions.免疫治疗中的表型和靶向药物发现:挑战、机遇与未来方向。
RSC Adv. 2025 Aug 22;15(36):29937-29951. doi: 10.1039/d5ra03914b. eCollection 2025 Aug 18.
2
A multiscale physiologically based pharmacokinetic model to support mRNA-encoded BiTE therapy in cancer treatment.一种基于生理的多尺度药代动力学模型,以支持mRNA编码的双特异性T细胞衔接器(BiTE)疗法用于癌症治疗。
Mol Ther Nucleic Acids. 2025 Jun 16;36(3):102606. doi: 10.1016/j.omtn.2025.102606. eCollection 2025 Sep 9.
3
One step further in targeting acute leukemia by combining antibody-based immunotherapies and small molecule inhibitors.

本文引用的文献

1
Recent advances of bispecific antibodies in solid tumors.双特异性抗体在实体瘤中的最新进展。
J Hematol Oncol. 2017 Sep 20;10(1):155. doi: 10.1186/s13045-017-0522-z.
2
Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn's disease and ulcerative colitis?免疫介导的炎症性疾病的新型治疗方法:从类风湿关节炎、脊柱关节炎、系统性红斑狼疮、银屑病、克罗恩病和溃疡性结肠炎的应用中我们可以学到什么?
Ann Rheum Dis. 2018 Feb;77(2):175-187. doi: 10.1136/annrheumdis-2017-211555. Epub 2017 Aug 1.
3
Pharmacokinetics of ABT-122, a TNF-α- and IL-17A-Targeted Dual-Variable Domain Immunoglobulin, in Healthy Subjects and Patients with Rheumatoid Arthritis: Results from Three Phase I Trials.
通过将基于抗体的免疫疗法与小分子抑制剂相结合,在靶向急性白血病方面更进一步。
Cancer Cell Int. 2025 Jul 7;25(1):254. doi: 10.1186/s12935-025-03869-w.
4
Passive Immunization in the Prevention and Treatment of Viral Infections.被动免疫在病毒感染预防与治疗中的应用
Eur J Immunol. 2025 May;55(5):e202451606. doi: 10.1002/eji.202451606.
5
Targeting DLL3: Innovative Strategies for Tumor Treatment.靶向DLL3:肿瘤治疗的创新策略。
Pharmaceutics. 2025 Apr 16;17(4):520. doi: 10.3390/pharmaceutics17040520.
6
Design and Characterization of Bispecific and Trispecific Antibodies Targeting SARS-CoV-2.靶向严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的双特异性和三特异性抗体的设计与表征
Vaccines (Basel). 2025 Feb 28;13(3):255. doi: 10.3390/vaccines13030255.
7
Assessing concentration in the monoclonal antibody innovation market: A patent-based study.评估单克隆抗体创新市场的集中度:一项基于专利的研究。
PLoS One. 2025 Mar 27;20(3):e0320864. doi: 10.1371/journal.pone.0320864. eCollection 2025.
8
10 years of BiTE immunotherapy: an overview with a focus on pancreatic cancer.双特异性T细胞衔接器(BiTE)免疫疗法十年综述:聚焦胰腺癌
Front Oncol. 2024 Dec 20;14:1429330. doi: 10.3389/fonc.2024.1429330. eCollection 2024.
9
A Comprehensive Review of the Mechanisms and Clinical Development of Monoclonal Antibodies in Cancer Therapy.癌症治疗中单克隆抗体的作用机制与临床进展综述
Adv Exp Med Biol. 2025;1479:181-203. doi: 10.1007/5584_2024_838.
10
End-To-End Automated Intact Protein Mass Spectrometry for High-Throughput Screening and Characterization of Bispecific and Multispecific Antibodies.用于双特异性和多特异性抗体高通量筛选和表征的全长蛋白质质谱分析的端到端自动化
Anal Chem. 2024 Nov 12;96(45):18287-18300. doi: 10.1021/acs.analchem.4c04833. Epub 2024 Oct 31.
ABT-122,一种针对 TNF-α 和 IL-17A 的双可变域免疫球蛋白,在健康受试者和类风湿关节炎患者中的药代动力学:三项 I 期临床试验结果。
Clin Pharmacokinet. 2018 May;57(5):613-623. doi: 10.1007/s40262-017-0580-y.
4
Chemically generated IgG2 bispecific antibodies through disulfide bridging.通过二硫键桥接化学合成的IgG2双特异性抗体。
Bioorg Med Chem Lett. 2017 Aug 15;27(16):3647-3652. doi: 10.1016/j.bmcl.2017.07.021. Epub 2017 Jul 8.
5
Polyfunctional response by ImmTAC (IMCgp100) redirected CD8 and CD4 T cells.ImmTAC(IMCgp100)重定向的CD8和CD4 T细胞的多功能反应。
Immunology. 2017 Nov;152(3):425-438. doi: 10.1111/imm.12779. Epub 2017 Aug 2.
6
Oncolytic adenovirus expressing bispecific antibody targets T-cell cytotoxicity in cancer biopsies.表达双特异性抗体的溶瘤腺病毒靶向癌症活检中的T细胞细胞毒性。
EMBO Mol Med. 2017 Aug;9(8):1067-1087. doi: 10.15252/emmm.201707567.
7
Correlates of resistance and relapse during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia.在blinatumomab 治疗复发/难治性急性淋巴细胞白血病期间,耐药和复发的相关性。
Am J Hematol. 2017 Sep;92(9):858-865. doi: 10.1002/ajh.24783. Epub 2017 Jun 5.
8
The development of bispecific antibodies and their applications in tumor immune escape.双特异性抗体的发展及其在肿瘤免疫逃逸中的应用。
Exp Hematol Oncol. 2017 May 2;6:12. doi: 10.1186/s40164-017-0072-7. eCollection 2017.
9
Clinical Pharmacology and Translational Aspects of Bispecific Antibodies.双特异性抗体的临床药理学与转化研究方面
Clin Transl Sci. 2017 May;10(3):147-162. doi: 10.1111/cts.12459. Epub 2017 Mar 15.
10
Translation and Clinical Development of Bispecific T-cell Engaging Antibodies for Cancer Treatment.用于癌症治疗的双特异性T细胞衔接抗体的翻译与临床开发
Clin Pharmacol Ther. 2017 May;101(5):634-645. doi: 10.1002/cpt.651.