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免疫球蛋白 γ 样治疗性双特异性抗体格式用于肿瘤治疗。

Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy.

机构信息

National Clinical Research Center for Normal Aging and Geriatric & Department of Oncology & Institute of Geriatric & The Key Lab of Normal Aging and Geriatric, The Second Medical Centre, PLA General Hospital, Beijing, China.

Medical of School & Graduate School, Nankai University, Tianjin, China.

出版信息

J Immunol Res. 2019 Feb 11;2019:4516041. doi: 10.1155/2019/4516041. eCollection 2019.


DOI:10.1155/2019/4516041
PMID:30886871
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6388348/
Abstract

Bispecific antibodies (BsAbs) are a sort of dual functional proteins with specific binding to two distinct targets, which have become a focus of interest in antibody engineering and drug development research and have a promising future for wide applications in cancer immunotherapy and autoimmune disease. The key of clinical application and commercial-scale manufacturing of BsAbs is the amenability to assembly and purification of desired heterodimers. Advances in genetic engineering technology had resulted in the development of diverse BsAbs. Multiple recombinant strategies have been used to solve the mispairing problem between light and heavy chains, as well as to enforce accurate dimerization of heterologous heavy chains. There are 23 platforms available to generate 62 BsAbs which can be further divided into IgG-like ones and fragment-based ones, and more than 50 molecules are undergoing clinical trials currently. BsAbs with IgG-like architecture exhibit superior advantages in structure (similar to natural antibodies), pharmacokinetics, half-life, FcR-mediated function, and biological activity. This review considers various IgG-like BsAb generation approaches, summarizes the clinical applications of promising new BsAbs, and describes the mechanism of BsAbs in tumor therapy.

摘要

双特异性抗体(BsAbs)是一类具有特异性结合两个不同靶标的双功能蛋白,已成为抗体工程和药物开发研究的热点,在癌症免疫治疗和自身免疫性疾病中有广泛应用的前景。BsAbs 临床应用和商业化生产的关键是具有期望异源二聚体组装和纯化的能力。基因工程技术的进步已经产生了多种 BsAbs。已经使用多种重组策略来解决轻链和重链之间的错配问题,并强制异源重链的准确二聚化。有 23 个平台可用于生成 62 种 BsAbs,它们可以进一步分为 IgG 样和基于片段的 BsAbs,目前有超过 50 种分子正在进行临床试验。具有 IgG 样结构的 BsAbs 在结构(类似于天然抗体)、药代动力学、半衰期、FcR 介导的功能和生物活性方面具有优势。本文综述了各种 IgG 样 BsAb 的生成方法,总结了有前途的新型 BsAbs 的临床应用,并描述了 BsAbs 在肿瘤治疗中的作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c18c/6388348/418f7836b377/JIR2019-4516041.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c18c/6388348/418f7836b377/JIR2019-4516041.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c18c/6388348/418f7836b377/JIR2019-4516041.001.jpg

相似文献

[1]
Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy.

J Immunol Res. 2019-2-11

[2]
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[3]
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[5]
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[6]
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[7]
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引用本文的文献

[1]
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Int J Biol Sci. 2025-1-27

[2]
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[3]
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[4]
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[5]
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[6]
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本文引用的文献

[1]
Phase I Trial of Anti-Vascular Endothelial Growth Factor/Anti-angiopoietin 2 Bispecific Antibody RG7716 for Neovascular Age-Related Macular Degeneration.

Ophthalmol Retina. 2017

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Avidity-based binding to HER2 results in selective killing of HER2-overexpressing cells by anti-HER2/CD3.

Sci Transl Med. 2018-10-17

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Invest New Drugs. 2018-9-19

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Bispecific antibodies in cancer immunotherapy.

Ther Adv Vaccines Immunother. 2018-2

[5]
Phase II Study of ABT-122, a Tumor Necrosis Factor- and Interleukin-17A-Targeted Dual Variable Domain Immunoglobulin, in Patients With Psoriatic Arthritis With an Inadequate Response to Methotrexate.

Arthritis Rheumatol. 2018-11

[6]
CD20-TCB with Obinutuzumab Pretreatment as Next-Generation Treatment of Hematologic Malignancies.

Clin Cancer Res. 2018-5-1

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Blood Rev. 2018-2-20

[8]
Bispecific antibodies: design, therapy, perspectives.

Drug Des Devel Ther. 2018-1-22

[9]
Therapeutic bispecific antibody formats: a patent applications review (1994-2017).

Expert Opin Ther Pat. 2018-3

[10]
Antibodies to watch in 2018.

MAbs. 2018-1-16

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