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一种新型的人源抗肿瘤二聚体免疫核糖核酸酶。

A novel human antitumor dimeric immunoRNase.

作者信息

Riccio Gennaro, Borriello Marianna, D'Alessio Giuseppe, De Lorenzo Claudia

机构信息

Dipartimento di Biologia Strutturale e Funzionale, Università di Napoli Federico II, Napoli, Italy.

出版信息

J Immunother. 2008 Jun;31(5):440-5. doi: 10.1097/CJI.0b013e31816bc769.

Abstract

We report on the construction, production, and characterization of a new fully human dimeric immunoRNase, obtained by fusion of Erbicin, a human anti-ErbB2 single-chain antibody fragment (scFv), with a dimeric mutant of human pancreatic RNase (HHP2-RNase). This novel immunoagent with 2 scFv moieties each fused to 1 of the 2 subunits of the dimeric RNase, called ERB-HHP2-RNase, has shown improved biologic properties with respect to the previously reported monomeric ERB-hRNase immunoRNase: it selectively binds ErbB2-positive cancer cells with an increased avidity; it is not inhibited by the cytosolic ribonuclease inhibitor; it is endowed with a more powerful cytotoxic activity.

摘要

我们报告了一种新型全人源二聚体免疫核糖核酸酶的构建、生产及特性,该酶通过将人抗ErbB2单链抗体片段(scFv)Erbicin与人类胰腺核糖核酸酶的二聚体突变体(HHP2-RNase)融合获得。这种新型免疫制剂有两个scFv部分,分别与二聚体核糖核酸酶的两个亚基之一融合,称为ERB-HHP2-RNase,与先前报道的单体ERB-hRNase免疫核糖核酸酶相比,它显示出更好的生物学特性:它以更高的亲和力选择性结合ErbB2阳性癌细胞;它不受胞质核糖核酸酶抑制剂的抑制;它具有更强的细胞毒性活性。

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