ELPylated anti-human TNF therapeutic single-domain antibodies for prevention of lethal septic shock

被引：85

作者：

Conrad, Udo ^{[2
]}

Plagmann, Ingo ^{[1
]}

Malchow, Sven ^{[1
]}

Sack, Markus ^{[3
]}

Floss, Doreen M. ^{[1
]}

Kruglov, Andrei A. ^{[4
]}

Nedospasov, Sergei A. ^{[4
,5
]}

Rose-John, Stefan ^{[1
]}

Scheller, Juergen ^{[1
]}

机构：

[1] Univ Kiel, Inst Biochem, D-2300 Kiel, Germany

[2] Inst Plant Genet & Crop Plant Res IPK, Gatersleben, Germany

[3] Rhein Westfal TH Aachen, Inst Mol Biotechnol, Aachen, Germany

[4] German Rheumatism Res Ctr DRFZ, Leibniz Inst, Berlin, Germany

[5] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, Russia

来源：

PLANT BIOTECHNOLOGY JOURNAL | 2011年 / 9卷 / 01期

关键词：

tumour necrosis factor; VHH; transgenic plants; elastin-like polypeptides; sepsis; nanobody; TRANSGENIC PLANTS; RHEUMATOID-ARTHRITIS; GENERAL STRATEGY; FUSION PROTEINS; CROHNS-DISEASE; IN-VIVO; ELASTIN; PURIFICATION; EXPRESSION; TOBACCO;

D O I：

10.1111/j.1467-7652.2010.00523.x

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Tumour necrosis factor (TNF) is a major pro-inflammatory cytokine involved in multiple inflammatory diseases. The detrimental activity of TNF can be blocked by various antagonists, and commercial therapeutics based upon this principle have been approved for treatment of diseases including rheumatoid arthritis, Crohn's disease and psoriasis. In a search for new, improved anti-inflammatory therapeutics we have designed a single-domain monoclonal antibody (VHH), which recognizes TNF. The antibody component (TNF-VHH) is based upon an anti-human TNF Camelidae heavy-chain monoclonal antibody, which was linked to an elastin-like polypeptide (ELP). We demonstrate that ELP fusion to the TNF-VHH enhances accumulation of the fusion protein during biomanufacturing in transgenic tobacco plants. With this study, we show for the first time that this plant-derived anti-human TNF-VHH antibody was biologically active in vivo. Therefore, therapeutic application of TNF-VHH-ELP fusion protein was tested in humanized TNF mice and was shown to be effective in preventing death caused by septic shock. The in vivo persistence of the ELPylated antibody was similar to 24 fold longer than that of non-ELPylated TNF-VHH.

引用

页码：22 / 31

页数：10

共 64 条

[1]

[Anonymous], 2012, Molecular Cloning: A Laboratory Manual

[2] EXPRESSION OF A SINGLE-CHAIN FV ANTIBODY AGAINST ABSCISIC-ACID CREATES A WILTY PHENOTYPE IN TRANSGENIC TOBACCO [J].