E-selectin is a viable route of infection for polymer-coated adenovirus retargeting in TNF-α-activated human umbilical vein endothelial cells

Mark Stevenson, Vladimir Subr, Leonard W. Seymour, Kerry Fisher, Houria Bachtarzi

Research output: Contribution to journalArticle

Abstract

E-selectin is an attractive endothelial cell surface marker in inflammation and cancer. Purpose: We sought to investigate retargeting of adenovirus via E-selectin as a viable pathway of infection in tumor necrosis factor-α (TNF-α)-activated human umbilical vein endothelial cells (HUVECs). Methods: E1, E3-deleted Ad5 expressing cytomegalovirus immediate-early (CMV IE) promoter-driven luciferase (Adluc) was coated with an amino-reactive multivalent hydrophilic polymer based on poly [N-(2-hydroxypropyl) methacrylamide] to generate pHPMA-adenovirus (pcAdluc). This was then retargeted by covalent attachment of a mouse antihuman E-selectin monoclonal antibody (MHES mAb), purified from the H18/7 hybridoma cell line (MHESpcAdluc). Results E-selectin positive cells but not in untreated receptor-negative cells. Specific retargeting of MHESpcAdluc was demonstrated through reduced transduction of stimulated HUVEC when incubated in the presence of free E-selectin antibodies.: MHESpcAdluc was efficiently taken up into HUVECs, generating a high level of transduction in TNF-α-treated Discussion and conclusion internalizing polymer-coated modified adenovirus particles through a viable receptor-mediated endocytosis pathway, generating adequate levels of transgene expression per virus genome copy without compromising the specific activity of the parental virus.: Our results suggest that E-selectin could be a valuable target for gene transfer strategies
Original languageEnglish
Pages (from-to)690-700
Number of pages11
JournalJournal of Drug Targeting
Volume19
Issue number8
Publication statusPublished - 1 Sep 2011

Keywords

  • Polymer-coated virus
  • vascular targeting
  • inflammation
  • cancer

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