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开发了第一类抗体和针对α-1,6-fucosylated前列腺特异抗原的特定测试

Steinar Halldórsson¹, Lars Hillringhaus², Caroline Hojer²

¹Pharma Research and Early Development, F. Hoffmann-La Roche AG, Basel, Switzerland.

Scientific reports

|July 17, 2024

概括

开发一种新型抗体,向基化前列腺特异性抗原 (fuc-PSA),为改善前列腺癌诊断提供了一个有前途的途径. 这种新工具提高了特异性,可能减少与当前PSA查相关的过度诊断和过度治疗.

科学领域:

生物化学生物化学
免疫学免疫学免疫学
在瘤学瘤学.

背景情况:

前列腺特异性抗原 (PSA) 查前列腺癌的准确性较低,导致过度诊断和过度治疗.
糖基化模式,特别是基化,代表了开发更精确的PSA生物标志物的潜在途径.

研究的目的:

为了产生一种特定的单克隆抗体 (mAb),向α-1,6-化PSA (fuc-PSA).
开发一种基于组织的检测方法来检测fuc-PSA.

主要方法:

用fuc-PSA免疫原体进行免疫,以产生单克隆抗体.
使用糖结合试验,表面等离子体共振和X射线晶体学对mAbs的表征.
在患者样本和甲固定,嵌组织中进行验证.

主要成果:

开发出一流的mAbs,具有对fuc-PSA的特异反应性,而不是对糖化PSA或无PSA甘的特异反应性.
证明了蛋白质展开对于患者样本中的fuc-PSA检测是必要的.
在组织样本中确认了表位特异性,表明了诊断应用的潜力.

结论:

已经产生了针对fuc-PSA的特征良好的抗体.
该研究提出了首个抗体的晶体结构,具有糖化特异性结的抗体.
这项工作为改善前列腺癌的糖化感知诊断工具奠定了基础.

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