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双特异性抗体武装的T细胞靶向癌细胞。

Bispecific Antibody Armed T Cells to Target Cancer Cells.

作者信息

Thakur Archana, Lum Lawrence G, Mittal Sandeep

机构信息

Division of Hematology/Oncology, Department of Medicine, University of Virginia Cancer Center, Charlottesville, VA, USA.

Department of Neurosurgery, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.

出版信息

Methods Mol Biol. 2018;1722:117-126. doi: 10.1007/978-1-4939-7553-2_8.

DOI:10.1007/978-1-4939-7553-2_8
PMID:29264802
Abstract

The common strategy for making bispecific antibodies (BsAbs) involves combining the variable domains of the desired monoclonal antibodies (mAbs) into a single bispecific structure. Bispecific immunotherapeutics has generated many different formats of BsAbs including chemical heteroconjugation of two complete molecules or fragments of monoclonal antibodies, quadroma, F(ab), diabodies, tandem diabodies, and single-chain antibodies (scFv). This chapter describes the process of generating activated T cells and arming T cells with heteroconjugated BsAbs to target cancer cells.

摘要

制备双特异性抗体(BsAb)的常见策略是将所需单克隆抗体(mAb)的可变结构域组合成单一的双特异性结构。双特异性免疫疗法已产生了多种不同形式的双特异性抗体,包括两个完整单克隆抗体分子或片段的化学异源缀合、四瘤、F(ab)、双抗体、串联双抗体和单链抗体(scFv)。本章描述了激活T细胞并用异源缀合的双特异性抗体武装T细胞以靶向癌细胞的过程。

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1
Bispecific Antibody Armed T Cells to Target Cancer Cells.双特异性抗体武装的T细胞靶向癌细胞。
Methods Mol Biol. 2018;1722:117-126. doi: 10.1007/978-1-4939-7553-2_8.
2
Cancer therapy with bispecific antibodies: Clinical experience.双特异性抗体癌症治疗:临床经验
Curr Opin Mol Ther. 2010 Jun;12(3):340-9.
3
Overcoming tumor heterogeneity by ex vivo arming of T cells using multiple bispecific antibodies.通过使用多种双特异性抗体对 T 细胞进行体外武装来克服肿瘤异质性。
J Immunother Cancer. 2022 Jan;10(1). doi: 10.1136/jitc-2021-003771.
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Structural design of disialoganglioside GD2 and CD3-bispecific antibodies to redirect T cells for tumor therapy.双唾液酸神经节苷脂GD2与CD3双特异性抗体的结构设计,用于重定向T细胞进行肿瘤治疗。
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Activated T cells armed with bispecific antibodies kill tumor targets.携带双特异性抗体的活化T细胞可杀死肿瘤靶点。
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Fab-based bispecific antibody formats with robust biophysical properties and biological activity.具有强大生物物理特性和生物活性的基于Fab的双特异性抗体形式。
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Design, selection and optimization of an anti-TRAIL-R2/anti-CD3 bispecific antibody able to educate T cells to recognize and destroy cancer cells.设计、选择和优化一种能够诱导 T 细胞识别和杀伤癌细胞的抗 TRAIL-R2/抗 CD3 双特异性抗体。
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Rearranging the domain order of a diabody-based IgG-like bispecific antibody enhances its antitumor activity and improves its degradation resistance and pharmacokinetics.重新排列基于双抗体的IgG样双特异性抗体的结构域顺序可增强其抗肿瘤活性,并提高其抗降解能力和药代动力学特性。
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BioDrugs. 2013 Feb;27(1):35-53. doi: 10.1007/s40259-012-0008-z.

引用本文的文献

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T-cell surface generation of dual bivalent, bispecific T-cell engaging, RNA duplex cross-linked antibodies (dbBiTERs) for re-directed tumor cell lysis.T 细胞表面生成双价、双特异性 T 细胞结合、RNA 双链交联抗体(dbBiTERs),用于重定向肿瘤细胞裂解。
Biotechnol J. 2022 Feb;17(2):e2100389. doi: 10.1002/biot.202100389. Epub 2021 Nov 25.
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Molecular imaging reveals biodistribution of P-cadherin LP-DART bispecific and trafficking of adoptively transferred T cells in mouse xenograft model.分子成像揭示了P-钙黏蛋白LP-DART双特异性分子在小鼠异种移植模型中的生物分布以及过继转移T细胞的转运情况。
Oncotarget. 2020 Apr 14;11(15):1344-1357. doi: 10.18632/oncotarget.27544.
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Integrin β4-Targeted Cancer Immunotherapies Inhibit Tumor Growth and Decrease Metastasis.
整合素 β4 靶向癌症免疫疗法抑制肿瘤生长并减少转移。
Cancer Res. 2020 Feb 15;80(4):771-783. doi: 10.1158/0008-5472.CAN-19-1145. Epub 2019 Dec 16.