新型重组抗HER2/neu免疫毒素：设计与抗肿瘤效率。

Novel recombinant anti-HER2/neu immunotoxin: design and antitumor efficiency.

作者信息

Sokolova E A, Zdobnova T A, Stremovskiy O A, Balalaeva I V, Deyev S M

机构信息

Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, 603950, Russia.

出版信息

Biochemistry (Mosc). 2014 Dec;79(12):1376-81. doi: 10.1134/S0006297914120128.

DOI:10.1134/S0006297914120128

PMID:25716732

Abstract

The novel HER2/neu-specific recombinant immunotoxin 4D5scFv-PE40 consisting of 4D5scFv antibody (targeting module) and Pseudomonas exotoxin A fragment (effector module) combined in a single polypeptide chain via a flexible linker has been expressed and purified. This immunotoxin conserves specificity and affinity that are characteristics of the parental antibody 4D5scFv and exhibits selective and strong cytotoxic effect against cancer cells overexpressing HER2/neu receptor. The results of the experiments both in vitro (in cell cultures) and in vivo (in tumor-bearing animals) demonstrate high potential of 4D5scFv-PE40 for targeted therapy of tumors overexpressing HER2/neu.

摘要

由4D5scFv抗体（靶向模块）和绿脓杆菌外毒素A片段（效应模块）通过柔性接头组合在一条多肽链中组成的新型HER2/neu特异性重组免疫毒素4D5scFv-PE40已被表达和纯化。这种免疫毒素保留了亲本抗体4D5scFv的特异性和亲和力，并对过表达HER2/neu受体的癌细胞表现出选择性和强烈的细胞毒性作用。体外（细胞培养）和体内（荷瘤动物）实验结果表明，4D5scFv-PE40在过表达HER2/neu肿瘤的靶向治疗中具有很高的潜力。