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学科主题: 临床医学
题名:
Effects of interlinker sequences on the biological properties of bispecific single-chain antibodies
作者: Fang, M; Jiang, X; Yang, Z; Yin, CC; Li, H; Zhao, R; Zhang, Z; Lin, Q; Huang, HL
关键词: single-chain antibody ; bispecific antibody ; single-chain bispecific antibody ; interlinker
刊名: CHINESE SCIENCE BULLETIN
发表日期: 2003-11-01
DOI: 10.1360/03wc0168
卷: 48, 期:21, 页:2277-2283
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: THERAPY ; DIABODY ; TETRAVALENT ; RETENTION ; MOLECULES ; BIVALENT ; HER2/NEU ; CANCER ; FV
英文摘要:

Single-chain bispecific antibody (scBsAb) is one of the promising genetic engineering antibody formats for clinical application. But the effects of interlinker sequences on the biological properties of bispecific single-chain antibodies have not been studied in deta it. Three interlinker sequences were designed and synthesized, and denominated as Fc, HSA, 205C′, respectively. Universal vectors with these different interlinker sequences for scBsAb expression in E. coli were constructed. A model scBsAb based on a reshaped single-chain antibody (scFv) against human CD3 and a scFv directed against human ovarian carcinoma were generated and expressed in E. coli. The results of SDS-PAGE and Western blot showed that the different interlinker sequences did not affect the expression level of scBsAb. However, as demonstrated by ELISA and pharmacokinetics studies performed in juice, scBsAbs with different interlinker sequences had difference in the antigen-binding activities and terminal half-life time (T-1/2beta) in vivo, the interlinker HSA could remarkably prolong the retention time of scBsAb in blood. These results indicated that the peptide sequence of interlinker could affect important biological properties of scBsAb, such as antigen-binding properties and stability ill vivo. So, selection of an appropriate interlinker sequence is very important for scBsAb construction. Optimal interlinker can bring scBsAb biological properties more suitable for clinical application.

语种: 英语
WOS记录号: WOS:000186533700002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56958
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: 1.Peking Univ, Sch Oncol, Beijing 100036, Peoples R China
2.Beijing Canc Hosp, Beijing 100036, Peoples R China
3.Acad Sinica, Inst Genet & Dev Biol, Beijing 100101, Peoples R China

Recommended Citation:
Fang, M,Jiang, X,Yang, Z,et al. Effects of interlinker sequences on the biological properties of bispecific single-chain antibodies[J]. CHINESE SCIENCE BULLETIN,2003,48(21):2277-2283.
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