Anti-serum albumin domain antibodies for extending the half-lives of short lived drugs

被引：151

作者：

Holt, Lucy J. ^{[1
]}

Basran, Amrik ^{[1
]}

Jones, Kate ^{[1
]}

Chorlton, Jennifer ^{[1
]}

Jespers, Laurent S. ^{[1
]}

Brewis, Neil D. ^{[1
]}

Tomlinson, Ian M. ^{[1
]}

机构：

[1] Domantis Ltd, Cambridge CB4 0WG, England

来源：

PROTEIN ENGINEERING DESIGN & SELECTION | 2008年 / 21卷 / 05期

关键词：

AlbudAb; albumin; domain antibody; half-life; dAb;

D O I：

10.1093/protein/gzm067

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have used phage display to isolate a range of human domain antibodies (dAbs) that bind to mouse, rat and/or human serum albumin (SA) and can be expressed at very high levels in bacterial, yeast or mammalian cell culture. In contrast to non-SA-binding dAbs, which have terminal half-lives of less than 45 min, the half-lives of these 12 kDa `AlbudAbs' can match the half-life of SA itself. To demonstrate the use of AlbudAbs for extending the half-lives of therapeutic drugs, we created a fusion of the interleukin-1 receptor antagonist (IL-1ra) with an AlbudAb. Soluble IL-1ra is potent inhibitor of IL-1 signalling that is approved for the treatment of rheumatoid arthritis but has a relatively short in vivo half-life. Here we show that although the AlbudAb/IL-1ra fusion has a similar in vitro potency, its in vivo efficacy can be dramatically improved due to its extended serum half-life. AlbudAbs could potentially be used to generate a range of long half-life versions of many different drugs in order to improve their dosing regimen and/or clinical effect.

引用

页码：283 / 288

页数：6

共 34 条

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