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构建一种对过表达c-erbB-2的癌症具有治疗潜力的嵌合抗体。

Construction of a chimeric antibody with therapeutic potential for cancers which overexpress c-erbB-2.

作者信息

Liu H L, Parkes D L, Langton B C, Xuan J A, Longhi M, Elliger S S, Chao L A, McGrogan M P, Brandis J W, Shawver L K

机构信息

Department of Cell and Molecular Biology, Berlex Biosciences, Richmond, CA, USA.

出版信息

Biochem Biophys Res Commun. 1995 Jun 26;211(3):792-803. doi: 10.1006/bbrc.1995.1882.

DOI:10.1006/bbrc.1995.1882
PMID:7598708
Abstract

We describe the chimerization of a monoclonal antibody directed against the c-erbB-2 protein using a novel PCR method for cloning immunoglobulin variable region genes. We also describe the characterization of the chimera and show its potential use for treating cancers which overexpress the c-erbB-2 protein. The genomic DNA fragments of heavy and light chain variable genes were cloned by PCR using uniquely designed primers which allowed for isolation of genes containing functional promoters, signal and coding sequences. The chimeric genes were then constructed by linking variable regions of murine genes to human constant gamma 1 and kappa genes. Expression of the chimeric immunoglobulin genes resulted in production of properly assembled chimeric antibody with improved biological properties.

摘要

我们描述了一种针对c-erbB-2蛋白的单克隆抗体的嵌合化过程,该过程使用一种新型PCR方法来克隆免疫球蛋白可变区基因。我们还描述了该嵌合体的特性,并展示了其在治疗过度表达c-erbB-2蛋白的癌症方面的潜在用途。使用独特设计的引物通过PCR克隆重链和轻链可变基因的基因组DNA片段,这些引物可用于分离包含功能性启动子、信号和编码序列的基因。然后通过将鼠源基因的可变区与人恒定γ1和κ基因连接来构建嵌合基因。嵌合免疫球蛋白基因的表达导致产生具有改善生物学特性的正确组装的嵌合抗体。

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