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双特异性抗体作为新型生物偶联物。

Bispecific antibodies as novel bioconjugates.

作者信息

Cao Y, Suresh M R

机构信息

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada, T6G 2N8.

出版信息

Bioconjug Chem. 1998 Nov-Dec;9(6):635-44. doi: 10.1021/bc980044l.

DOI:10.1021/bc980044l
PMID:9815155
Abstract

Bispecific antibodies are unique macromolecular heterobifunctional cross-linkers with two different binding specificities within a single molecule. As ideal bioconjugates, they can specifically glue any two different molecules together without the need for chemical conjugation. With this unique feature, they have immense potential in biological and immunological fields. Their applications range from immunohistochemistry, immunoassays, radioimmunodiagnosis, radioimmunotherapy, and immunotherapy. Recently, a new second generation of bispecific molecules, bispecific single chain Fv and diabodies, has been produced by DNA recombinant technology. They can be considered as the ultimate magic bullets for in vivo applications. They may theoretically improve tumor or pathogen targeting and minimize side effects, eventually replacing the full-length bispecific antibodies. Emphasizing on developmental methodology and clinical applications of bispecific antibodies, this review gives a bird's-eye view of these unique bioconjugates.

摘要

双特异性抗体是独特的大分子异双功能交联剂,在单个分子内具有两种不同的结合特异性。作为理想的生物共轭物,它们可以特异性地将任何两种不同的分子粘合在一起,而无需化学共轭。凭借这一独特特性,它们在生物学和免疫学领域具有巨大潜力。其应用范围涵盖免疫组织化学、免疫测定、放射免疫诊断、放射免疫治疗和免疫治疗。最近,通过DNA重组技术产生了新一代双特异性分子,即双特异性单链Fv和双抗体。它们可被视为体内应用的终极神奇药物。从理论上讲,它们可以改善肿瘤或病原体靶向性并将副作用降至最低,最终取代全长双特异性抗体。本文着重介绍双特异性抗体的研发方法和临床应用,对这些独特的生物共轭物进行了全景式的综述。

相似文献

1
Bispecific antibodies as novel bioconjugates.双特异性抗体作为新型生物偶联物。
Bioconjug Chem. 1998 Nov-Dec;9(6):635-44. doi: 10.1021/bc980044l.
2
Recent advances in the generation of bispecific antibodies for tumor immunotherapy.用于肿瘤免疫治疗的双特异性抗体生成的最新进展。
Curr Opin Drug Discov Devel. 2004 Mar;7(2):233-42.
3
The assembly of single domain antibodies into bispecific decavalent molecules.单域抗体组装成双特异性十价分子。
J Immunol Methods. 2007 Jan 10;318(1-2):88-94. doi: 10.1016/j.jim.2006.10.006. Epub 2006 Nov 17.
4
Bispecific tandem diabody for tumor therapy with improved antigen binding and pharmacokinetics.用于肿瘤治疗的双特异性串联双体,具有改善的抗原结合能力和药代动力学特性。
J Mol Biol. 1999 Oct 15;293(1):41-56. doi: 10.1006/jmbi.1999.3156.
5
Generation of dual-variable-domain immunoglobulin molecules for dual-specific targeting.用于双特异性靶向的双可变域免疫球蛋白分子的生成。
Methods Enzymol. 2012;502:25-41. doi: 10.1016/B978-0-12-416039-2.00002-1.
6
Expression and purification of monospecific and bispecific recombinant antibody fragments derived from antibodies that block the CD80/CD86-CD28 costimulatory pathway.源自阻断CD80/CD86-CD28共刺激途径的抗体的单特异性和双特异性重组抗体片段的表达与纯化。
Protein Expr Purif. 2001 Jun;22(1):11-24. doi: 10.1006/prep.2001.1417.
7
Construction of optimized bispecific antibodies for selective activation of the death receptor CD95.用于选择性激活死亡受体CD95的优化双特异性抗体的构建。
Cancer Res. 2008 Feb 15;68(4):1221-7. doi: 10.1158/0008-5472.CAN-07-6175.
8
Bispecific antibodies: molecules that enable novel therapeutic strategies.双特异性抗体:实现新型治疗策略的分子。
Pathobiology. 2007;74(1):3-14. doi: 10.1159/000101046.
9
Preparation and biomedical applications of bispecific antibodies.双特异性抗体的制备及其生物医学应用
Behring Inst Mitt. 1985 Dec(78):118-32.
10
Phage diabody repertoires for selection of large numbers of bispecific antibody fragments.用于筛选大量双特异性抗体片段的噬菌体双体文库。
Nat Biotechnol. 1996 Sep;14(9):1149-54. doi: 10.1038/nbt0996-1149.

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A detergent-based procedure for the preparation of IgG-like bispecific antibodies in high yield.一种基于去污剂的高产量 IgG 样双特异性抗体制备方法。
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An in vitro demonstration of overcoming drug resistance in SKOV3 TR and MCF7 ADR with targeted delivery of polymer pro-drug conjugates.通过聚合物前药偶联物的靶向递送在SKOV3 TR和MCF7 ADR中克服耐药性的体外证明。
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