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十种抗前列腺特异性抗原单克隆抗体与人腺体激肽释放酶的交叉反应性。

Cross-reactivity of ten anti-prostate-specific antigen monoclonal antibodies with human glandular kallikrein.

作者信息

Corey E, Buhler K R, Vessella R L

机构信息

Tumor Immunology Laboratory of the Urology Department, Medical School, University of Washington, Seattle 98195, USA.

出版信息

Urology. 1997 Oct;50(4):567-71; discussion 571-2. doi: 10.1016/S0090-4295(97)00415-9.

DOI:10.1016/S0090-4295(97)00415-9
PMID:9338733
Abstract

OBJECTIVES

Prostate-specific antigen (PSA) is commonly used as a marker for prostate disease. Prostate epithelium expresses both PSA and human glandular kallikrein (hK2) proteins, which share 80% sequence homology. The immunologic cross-reactivity of these two proteins could potentially interfere with determination of PSA levels in diagnoses of prostate cancer. We set out to determine the extent of this cross-reactivity for a panel of 10 anti-PSA monoclonal antibodies (mAbs).

METHODS

Enzyme-linked immunosorbent assay (ELISA), sandwich assays, and western transfer techniques were used to assess the PSA/hK2 cross-reactivity of the anti-PSA mAbs.

RESULTS

We did not detect the hK2 protein with any of the 10 anti-PSA mAbs under western transfer conditions. In ELISA experiments, 8 of 10 mAbs exhibited hK2 cross-reactivity under certain conditions. However, no combination of mAbs tested in sandwich assays exhibited a signal in hK2 cross-reactivity experiments greater than 0.1% of the PSA signal.

CONCLUSIONS

We have evaluated 10 anti-PSA mAbs and determined that despite the 80% homology between PSA and hK2 proteins, cross-reactivity with hK2 by these antibodies would not significantly affect the determination of PSA levels by means of sandwich assays.

摘要

目的

前列腺特异性抗原(PSA)常用于前列腺疾病的标志物。前列腺上皮细胞表达PSA和人腺激肽释放酶(hK2)蛋白,这两种蛋白的序列同源性为80%。这两种蛋白的免疫交叉反应性可能会干扰前列腺癌诊断中PSA水平的测定。我们着手确定一组10种抗PSA单克隆抗体(mAb)的这种交叉反应性程度。

方法

采用酶联免疫吸附测定(ELISA)、夹心测定法和western印迹技术评估抗PSA mAb的PSA/hK2交叉反应性。

结果

在western印迹条件下,我们用10种抗PSA mAb中的任何一种均未检测到hK2蛋白。在ELISA实验中,10种mAb中有8种在某些条件下表现出hK2交叉反应性。然而,在夹心测定法中测试的mAb组合在hK2交叉反应性实验中均未显示出大于PSA信号0.1%的信号。

结论

我们评估了10种抗PSA mAb,并确定尽管PSA和hK2蛋白之间有80%的同源性,但这些抗体与hK2的交叉反应性不会显著影响通过夹心测定法测定PSA水平。

相似文献

1
Cross-reactivity of ten anti-prostate-specific antigen monoclonal antibodies with human glandular kallikrein.十种抗前列腺特异性抗原单克隆抗体与人腺体激肽释放酶的交叉反应性。
Urology. 1997 Oct;50(4):567-71; discussion 571-2. doi: 10.1016/S0090-4295(97)00415-9.
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Generation of monoclonal antibodies specific for human kallikrein 2 (hK2) using hK2-expressing tumors.利用表达人激肽释放酶2(hK2)的肿瘤生成针对hK2的单克隆抗体。
Prostate. 2002 May 15;51(3):153-65. doi: 10.1002/pros.10071.
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Polyclonal and monoclonal antibodies to prostate-specific antigen can cross-react with human kallikrein 2 and human kallikrein 1.针对前列腺特异性抗原的多克隆抗体和单克隆抗体可与人激肽释放酶2和人激肽释放酶1发生交叉反应。
Urology. 1999 Apr;53(4):746-51. doi: 10.1016/s0090-4295(98)00573-1.
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Development of monoclonal antibodies specific for human glandular kallikrein (hK2): development of a dual antibody immunoassay for hK2 with negligible prostate-specific antigen cross-reactivity.人腺激肽释放酶(hK2)特异性单克隆抗体的研制:一种对前列腺特异性抗原交叉反应可忽略不计的hK2双抗体免疫测定法的研制
Urology. 1998 May;51(5):804-9. doi: 10.1016/s0090-4295(98)00107-1.
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Structural comparison of prostate-specific antigen and human glandular kallikrein using molecular modeling.利用分子建模对前列腺特异性抗原和人腺体激肽释放酶进行结构比较。
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Production of recombinant PSA and HK2 and analysis of their immunologic cross-reactivity.重组前列腺特异性抗原(PSA)和己糖激酶2(HK2)的制备及其免疫交叉反应性分析。
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Detection of human glandular kallikrein, hK2, as its precursor form and in complex with protease inhibitors in prostate carcinoma serum.在前列腺癌血清中检测人腺体激肽释放酶hK2及其前体形式以及与蛋白酶抑制剂形成的复合物。
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Expression of human glandular kallikrein, hK2, in mammalian cells.人腺激肽释放酶hK2在哺乳动物细胞中的表达。
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Determination and analysis of antigenic epitopes of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2) using synthetic peptides and computer modeling.利用合成肽和计算机建模对前列腺特异性抗原(PSA)和人腺体激肽释放酶2(hK2)的抗原表位进行测定和分析。
Protein Sci. 1998 Feb;7(2):259-69. doi: 10.1002/pro.5560070205.
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Molecular forms of prostate-specific antigen and human kallikrein 2 (hK2) in urine are not clinically useful for early detection and staging of prostate cancer.尿液中前列腺特异性抗原和人激肽释放酶2(hK2)的分子形式对前列腺癌的早期检测和分期在临床上并无用处。
Urology. 1997 Nov;50(5):715-21. doi: 10.1016/S0090-4295(97)00324-5.

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Expression of a prostate-associated protein, human glandular kallikrein (hK2), in breast tumours and in normal breast secretions.一种前列腺相关蛋白——人腺激肽释放酶(hK2)在乳腺肿瘤及正常乳腺分泌物中的表达。
Br J Cancer. 2000 Jan;82(2):361-7. doi: 10.1054/bjoc.1999.0927.
2
Prediction of gene function by genome-scale expression analysis: prostate cancer-associated genes.通过基因组规模表达分析预测基因功能:前列腺癌相关基因
Genome Res. 1999 Dec;9(12):1198-203. doi: 10.1101/gr.9.12.1198.