文献类型：期刊文献

英文题名：Transient gene expression of a mouse homolog of Fcε-Fcγ fusion protein for anti-allergic function assay

作者：Cheng, Lu[1];Sun, Xiangming[2];Yi, Xiaoping[1];Zhang, Yuanxing[1]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Fuchun Kexin Biotech Co Ltd, Shanghai 201203, Peoples R China

年份：2011

卷号：46

期号：4

起止页码：858

外文期刊名：PROCESS BIOCHEMISTRY

收录：;EI(收录号：20111013731595);WOS:【SCI-EXPANDED(收录号:WOS:000289396200005)】；

基金：This work was supported by grants from the Open Project Funding of State Key Laboratory of Bioreactor Engineering of China and National Special Project of Key Technology of China (2009ZX09503-013-2 and 2009ZX09102-249).

语种：英文

外文关键词：Anti-allergy fusion protein (AAFP); Transient gene expression; CHO cells; PCA

摘要：The Fc epsilon similar to Fc gamma fusion protein (AAFP) is considered as a promising drug candidate for IgE-mediated allergic diseases by bridging REM and Fc gamma RII together on mast cells and basophils. The coaggregation depends on the flexible IgG1 hinge in AAFP with a necessary spatial relationship between AAFP and its two receptors. In this work, a mouse homolog of AAFP (mAAFP) was designed and transiently expressed in Chinese hamster ovary cells to facilitate the evaluation of its efficacy in mouse. The parameters affecting transient gene expression (TGE) were optimized in 6-well plates, and then the process was conducted to produce 2 mg mAAFP in the batch culture in 1.31 bioreactor. To improve the production yield, fed-batch and hypothermic fed-batch cultures were adopted to achieve 5.5- and 14-fold increases, respectively. The obtained mAAFP was assayed in vivo in a mouse passive cutaneous anaphylaxis (PCA) model. The results showed that mAAFP significantly inhibited IgE-mediated allergic reaction and its efficacy lasted for at least 24 days. It is indicated that the IgG1 hinge could coaggregate Fc epsilon RI with the inhibitory receptor Fc gamma RII on mast cells and basophils, and thus activate the inhibitory signaling pathway of Fc gamma RII. This work shows AAFP has great potential for allergy therapy. (c) 2010 Elsevier Ltd. All rights reserved.