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一种通用的抗体衍生靶向剂。

A universal antibody-derived targeting agent.

作者信息

Spooner R A, Deonarain M P, Savage P, Epenetos A A

机构信息

Royal Postgraduate Medical School, Department of Clinical Oncology, Hammersmith Hospital, London.

出版信息

Cell Biophys. 1993 Jan-Jun;22(1-3):225-42. doi: 10.1007/BF03033875.

DOI:10.1007/BF03033875
PMID:7889540
Abstract

We report bacterial expression of a single-chain antibody (ScFv) reactive against the haptens 4-hydroxy-3 nitrophenylacetic acid (NP) and 4-hydroxy-3-iodo-5-nitrophenylacetic acid (NIP) that is suitable for targeting to mammalian cells in vitro in a novel two-step targeting strategy. Hapten-derivatized primary antibodies of known specificity, bound to target cells, can capture the ScFv. Specificity resides in the interaction of the primary targeting antibody with the target and the interaction of the ScFv for NP/NIP, since the ScFv does not bind cells and nonderivatized antibodies bound at cells cannot capture the ScFv. The ScFv described here can therefore be considered as a universal agent for delivery of drugs, toxins, or radionuclides to any cell type for which a previously characterized antibody exists.

摘要

我们报道了一种单链抗体(ScFv)的细菌表达,该抗体可与半抗原4-羟基-3-硝基苯乙酸(NP)和4-羟基-3-碘-5-硝基苯乙酸(NIP)发生反应,适用于一种新型两步靶向策略中的体外靶向哺乳动物细胞。与靶细胞结合的具有已知特异性的半抗原衍生化一抗可以捕获ScFv。特异性存在于一级靶向抗体与靶标的相互作用以及ScFv与NP/NIP的相互作用中,因为ScFv不结合细胞,且结合在细胞上的未衍生化抗体无法捕获ScFv。因此,这里描述的ScFv可被视为一种通用试剂,用于将药物、毒素或放射性核素递送至任何存在先前已鉴定抗体的细胞类型。

相似文献

1
A universal antibody-derived targeting agent.一种通用的抗体衍生靶向剂。
Cell Biophys. 1993 Jan-Jun;22(1-3):225-42. doi: 10.1007/BF03033875.
2
Construction, bacterial expression, and characterization of hapten-specific single-chain Fv and alkaline phosphatase fusion protein.半抗原特异性单链Fv与碱性磷酸酶融合蛋白的构建、细菌表达及特性分析
J Biochem. 1997 Aug;122(2):322-9. doi: 10.1093/oxfordjournals.jbchem.a021756.
3
The influence of antibody affinity on the radioallergosorbent test (RAST) and in vitro histamine release. Studies with hapten-specific monoclonal IgE antibodies.抗体亲和力对放射变应原吸附试验(RAST)及体外组胺释放的影响。对半抗原特异性单克隆IgE抗体的研究。
J Immunol Methods. 1986 May 22;89(2):249-55. doi: 10.1016/0022-1759(86)90365-0.
4
Role of conserved amino acid residues in the complementarity determining regions on hapten-antibody interaction of anti-(4-hydroxy-3-nitrophenyl) acetyl antibodies.保守氨基酸残基在抗(4-羟基-3-硝基苯基)乙酰抗体的半抗原-抗体相互作用的互补决定区中的作用。
Mol Immunol. 1995 Sep;32(13):983-90. doi: 10.1016/0161-5890(95)00057-l.
5
Murine lupus anti-DNA antibodies cross-react with the hapten (4-hydroxy-5-iodo-3-nitrophenyl)acetyl, but immunization-induced anti-DNA antibodies do not.小鼠狼疮抗DNA抗体与半抗原(4-羟基-5-碘-3-硝基苯基)乙酰发生交叉反应,但免疫诱导的抗DNA抗体则不会。
Eur J Immunol. 1987 Apr;17(4):509-13. doi: 10.1002/eji.1830170412.
6
4-Hydroxy-3-nitrophenyl (NP) acetyl-hapten specific lymphocyte proliferation. I. Mice bearing Igh-1b allotype can cross-react with 4-hydroxy-5-iodo-3-nitrophenyl (NIP) acetyl hapten.4-羟基-3-硝基苯基(NP)乙酰半抗原特异性淋巴细胞增殖。I. 携带Igh-1b同种异型的小鼠可与4-羟基-5-碘-3-硝基苯基(NIP)乙酰半抗原发生交叉反应。
Microbiol Immunol. 1984;28(4):471-9. doi: 10.1111/j.1348-0421.1984.tb00698.x.
7
Initial repertoire of anti-(4-hydroxy-3-nitrophenylacetyl) antibodies as potential donors for effective affinity maturation.作为有效亲和力成熟潜在供体的抗(4-羟基-3-硝基苯乙酰)抗体的初始库。
Mol Immunol. 2006 Apr;43(11):1751-60. doi: 10.1016/j.molimm.2005.11.009. Epub 2006 Jan 9.
8
Strategy for affinity maturation of an antibody with high evolvability to (4-hydroxy-3-nitrophenyl) acetyl hapten.针对具有高进化能力的抗体与(4-羟基-3-硝基苯基)乙酰半抗原进行亲和力成熟的策略。
Mol Immunol. 2007 Mar;44(9):2436-45. doi: 10.1016/j.molimm.2006.10.023. Epub 2006 Nov 21.
9
Fine specificity of cytotoxic T lymphocytes: C57BL effector cells induced by autologous cells modified with hapten (4-hydroxy-3-nitro-phenyl)acetyl (NIP) are not heteroclitic.细胞毒性T淋巴细胞的精细特异性:用半抗原(4-羟基-3-硝基苯基)乙酰基(NIP)修饰的自体细胞诱导产生的C57BL效应细胞不存在交叉反应。
Eur J Immunol. 1979 Mar;9(3):211-3. doi: 10.1002/eji.1830090308.
10
Specificity change of antibody to (4-hydroxy-3-nitrophenyl)acetyl haptens by somatic hypermutation.通过体细胞超突变对(4-羟基-3-硝基苯基)乙酰半抗原的抗体特异性变化
J Biochem. 1987 Dec;102(6):1337-43. doi: 10.1093/oxfordjournals.jbchem.a122179.

本文引用的文献

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A recombinant single chain antibody interleukin-2 fusion protein.一种重组单链抗体白细胞介素-2融合蛋白。
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Proc Natl Acad Sci U S A. 1988 Jul;85(13):4842-6. doi: 10.1073/pnas.85.13.4842.
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A cytotoxic agent can be generated selectively at cancer sites.一种细胞毒性剂可以在癌症部位被选择性地产生。
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Single-chain antigen-binding proteins.单链抗原结合蛋白
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