Targeting adenovirus gene delivery to activated tumour-associated vasculature via endothelial selectins

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

Research output: Contribution to journalArticle

Abstract

Clinical experience with adenovirus vectors has highlighted the need for improved delivery and targeting. Tumour-associated endothelium offers an additional mechanism for enhanced viral uptake into tumours which is accessible for systemic gene delivery. Building on expertise in using polymer‘stealthed’ viruses for targeting in vivo (2-hydroxypropyl) methacrylamide] to ablate normal infection pathways. Direct linkage of a monoclonal antibody against E-selectin (MHES) demonstrated E-selectin-speci, adenovirus expressing luciferase (Adluc) was coated with an amino-reactive polymer based on poly [N-fic transduction of tumour necrosis factor-α (TNF- provide optimal antibody orientation. We report an enhancement in transduction of TNF- endothelium virus retargeted using a chimeric P-selectin Glycoprotein Ligand-1-Fc fusion (PSGL-1) protein showed better circulation kinetics and signi with 36-fold higher genome copies, compared with non-modi tumour sections from mice treated with PSGL-1-retargeted virus showed a co-localisation of with CD31 suggesting selective endothelial targeting. Employment of optimal viral modi G will enable exploration and comparison of alternative targeting ligands targeting tumour-associated endothelium.α)-activated endothelial cells. A two-component targeting system using protein G was developed, toα-activatedin vitro and ex vivo in a human umbilical vein cord model using the MHES antibody. Similarly aficant uptake into HepG2 xenografts following systemic administration in mice,fied virus. Immunohistochemistry staining offirefly luciferasefication using protein
Original languageEnglish
Pages (from-to)196-203
Number of pages8
JournalJournal of Controlled Release
Volume150
Issue number2
Publication statusPublished - 10 Mar 2011

Keywords

  • E-selectin
  • pHPMA
  • Adenovirus
  • Vascular targeting
  • Cancer

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    Bachtarzi, H., Stevenson, M., Subr, V., Ulbrich, K., Seymour, L. W., & Fisher, K. (2011). Targeting adenovirus gene delivery to activated tumour-associated vasculature via endothelial selectins. Journal of Controlled Release, 150(2), 196-203.