Intravascularly administered RGD-displaying measles viruses bind to and infect neovessel endothelial cells in vivo

Hooi Tin Ong, Theodore R. Trejo, Linh D. Pham, Ann L Oberg, Stephen J Russell, Kah-Whye Peng

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Systemically administered vectors must cross the endothelial lining of tumor blood vessels to access cancer cells. Vectors that interact with markers on the lumenal surface of these endothelial cells might have enhanced tumor localization. Here, we generated oncolytic measles viruses (MVs) displaying αvβ3 integrin-binding peptides, cyclic arginine-glycine-aspartate (RGD) or echistatin, on the measles hemagglutinin protein. Both viruses had expanded tropisms, and efficiently entered target cells via binding to integrins, but also retained their native tropisms for CD46 and signaling lymphocyte activation molecule (SLAM). When fluorescently labeled and injected intravascularly into chick chorioallantoic membranes (CAMs), in contrast to unmodified viruses, the integrin-binding viral particles bound to the lumenal surface of the developing chick neovessels and infected the CAM vascular endothelial cells. In a mouse model of VEGF-induced angiogenesis in the ear pinna, the integrin-binding viruses, but not the parental virus, infected cells at sites of new blood vessel formation. When given intravenously to mice bearing tumor xenografts, the integrin-binding virus infected endothelial cells of tumor neovessels in addition to tumor parenchyma. To our knowledge, this is the first report demonstrating that oncolytic MVs can be engineered to target the lumenal endothelial surface of newly formed blood vessels when administered intravenously in living animals.

Original languageEnglish (US)
Pages (from-to)1012-1021
Number of pages10
JournalMolecular Therapy
Volume17
Issue number6
DOIs
StatePublished - 2009

Fingerprint

Measles virus
Integrins
Virus Attachment
Endothelial Cells
Oncolytic Viruses
Chorioallantoic Membrane
Tropism
Neoplasms
Blood Vessels
Ear Auricle
Vascular Tissue Neoplasms
Viruses
Cyclic Peptides
Measles
Hemagglutinins
Lymphocyte Activation
Heterografts
Virion
Glycine
Vascular Endothelial Growth Factor A

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

Cite this

Intravascularly administered RGD-displaying measles viruses bind to and infect neovessel endothelial cells in vivo. / Ong, Hooi Tin; Trejo, Theodore R.; Pham, Linh D.; Oberg, Ann L; Russell, Stephen J; Peng, Kah-Whye.

In: Molecular Therapy, Vol. 17, No. 6, 2009, p. 1012-1021.

Research output: Contribution to journalArticle

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