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新型前列腺特异性单克隆抗体的研发

Development of new prostate specific monoclonal antibodies.

作者信息

Lampe M I, Molkenboer-Kuenen J D M, Oosterwijk E

机构信息

Experimental Urology, Department of Urology, University Medical Center, Nijmegen, The Netherlands.

出版信息

Prostate. 2004 Feb 15;58(3):225-31. doi: 10.1002/pros.10326.

Abstract

BACKGROUND

Despite the need for new prostate-specific diagnostic and therapeutic targets, very few unique prostate (cancer) specific antigens have been characterized. Monoclonal antibody (mAb) technology is a powerful tool to identify specific antigenic markers, which could be potential targets for cancer diagnostics or therapy.

METHODS

Splenocytes from mice immunized with prostate cancer (PCa) homogenates of different origin were fused using standard techniques. Employing a differential high-throughput screening method followed by immediate screening in immunohistochemistry (IHC) a large number of hybridomas were screened for prostate (cancer) specificity.

RESULTS

From 25 successful fusions approximately 300 clones were identified excreting PCa-reactive antibodies. Subsequent immunohistochemical fine-specificity analysis reduced this number to 26. Eventually, after extensive fine-specificity analysis, the number of mAbs appearing to define prostate-specific antigenic structures that might serve as new diagnostic or therapeutic targets was reduced to three.

CONCLUSIONS

Using mAb technology combined with a high throughput screening method we have developed three mAbs (1.8, 2.26, and 3.10) directed against prostate associated antigens that might identify potential new therapeutic targets.

摘要

背景

尽管需要新的前列腺特异性诊断和治疗靶点,但已鉴定的独特前列腺(癌)特异性抗原却非常少。单克隆抗体(mAb)技术是识别特异性抗原标志物的有力工具,这些标志物可能是癌症诊断或治疗的潜在靶点。

方法

使用标准技术将用不同来源的前列腺癌(PCa)匀浆免疫的小鼠脾细胞进行融合。采用差异高通量筛选方法,随后立即进行免疫组织化学(IHC)筛选,对大量杂交瘤进行前列腺(癌)特异性筛选。

结果

从25次成功融合中鉴定出约300个分泌PCa反应性抗体的克隆。随后的免疫组织化学精细特异性分析将这一数量减少到26个。最终,经过广泛的精细特异性分析,似乎能定义可能作为新诊断或治疗靶点的前列腺特异性抗原结构的单克隆抗体数量减少到3个。

结论

通过将单克隆抗体技术与高通量筛选方法相结合,我们开发了三种针对前列腺相关抗原的单克隆抗体(1.8、2.26和3.10),它们可能识别潜在的新治疗靶点。

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