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Generation of a monoclonal human single chain antibody fragment to hepatic stellate cells--a potential mechanism for targeting liver anti-fibrotic therapeutics.

Abstract：

BACKGROUND/AIMS:Hepatic stellate cells are pivotal to fibrogenesis in the liver and many potential anti-fibrotic therapeutics are required to act on targets within hepatic stellate cells. The aim of this study was to generate a human antibody fragment to hepatic stellate cells. METHODS:Phage display was used to generate a human monoclonal antibody fragment to a peptide sequence present on an extracellular domain of synaptophysin, a protein expressed on the surface of hepatic stellate cells. RESULTS:An antibody fragment was isolated (termed C1-3), expressed in bacteria and purified. Fluorescently-labelled C1-3 antibody associated with human hepatic stellate cells but not hepatocytes in culture. Binding of fluorescently labelled C1-3 to hepatic stellate cells was blocked by the extracellular synaptophysin peptide sequence and uptake of the antibody intracellularly was inhibited by monensin. The toxin tributyl tin-when conjugated to C1-3-retained the ability to kill hepatic stellate cells confirming that C1-3 is sequestered intracellularly. CONCLUSIONS:This antibody fragment may be an effective means to target therapeutics to human hepatic stellate cells.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Elrick LJ,Leel V,Blaylock MG,Duncan L,Drever MR,Strachan G,Charlton KA,Koruth M,Porter AJ,Wright MC

doi

10.1016/j.jhep.2005.01.028

subject

Has Abstract

pub_date

2005-06-01 00:00:00

pages

888-96

issue

6

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(05)00184-4

journal_volume

42

pub_type

杂志文章

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